This is a compilation of articles published in the scientific literature in which Shetland Sheepdogs have been mentioned or were a significant part of the work. This is NOT intended to be an exhaustive, all-inclusive list. However, some conditions not found in the Health Section of the ASSA website might be found here. The intention is for this document to be updated periodically. In many instances, summaries are included as are online links to the articles. Articles are listed from most recent to oldest for each section.

Table of Content

Blood/lymph disorders
• Hypercholesterolemia
• vWD

• Oral tumors
• Testicular tumors

• Patent ductus arteriosus

Dental disorders
• Caudal crossbite
• Lance canine teeth

Endocrine disorders
• Thyroid

Liver/gallbladder disorders
• Gallbladder mucoceles
• Portosystemic shunts
• Other

Neurologic/muscular disorders
• Degenerative myelopathy
• Epilepsy
• MDR-1
• Other

• Collie eye anomaly
• Corneal dystrophy
• Progressive retinal atrophy
• Other

Orthopedic disorders
• Superficial digital flexor tendon injury
• Other

Reproductive Disorders
• Retrograde ejaculation
• Cryptorchidism

• Dermatomyositis
• Lupus

Urinary Tract
• Bladder cancer
• Renal disease

Blood/lymph disorders

• Hypercholesterolemia

Sato K, Agoh H, Kaneshige T, et al. Hypercholesterolemia in Shetland sheepdogs. J Vet Med Sci, 2000; 62:1297-1301.


Plasma lipoprotein cholesterol in 64 clinically healthy Shetland sheepdogs was evaluated to assess whether the breed is more susceptible to hypercholesterolemia. The incidence of hypercholesterolemia was clearly higher in Shetland sheepdogs and mean plasma cholesterol level was significantly higher in Shetland sheepdogs than in control dogs. Blood biochemical examinations did not evidence the abnormalities, which imply the causative disorders, and thyroid hormone levels were not significantly different from the controls. These results suggest that the cholesterolemia is a primary disorder. Cholesterol fractionation by agarose gel electrophoresis and ultracentrifugation revealed that accumulation of alpha2-migrating lipoproteins was the common characteristic of dogs showing cholesterol level over 250 mg/dl in the breed. Increase in prebeta-beta-lipoproteins was also found in Shetland sheepdogs with marked hypercholesterolemia over 500 mg/dl. Therefore, Shetland sheepdogs may include more dogs with primary disorders in lipoprotein metabolism, which cause hypercholesterolemia at least in Japan.

Department of Veterinary Internal Medicine, Faculty of Agriculture, Tottori University, Koyama, Japan.

• von Willebrand’s Disease

Brooks M, Dodds WJ, Raymond SL. Epidemiologic features of von Willebrand's disease in Doberman pinschers, Scottish terriers, and Shetland sheepdogs: 260 cases (1984-1988). J Am Vet Med Assoc, 1992; 200: 1123-1127.;jsessionid=TnyzueiJQErzkf6kHrm0.23


During a study period from 1985 through 1988, plasma von Willebrand's factor antigen (vWF:Ag) concentration was measured as a marker for prevalence of the von Willebrand's disease (vWD) trait in Doberman Pinschers (Doberman, n = 5,554), Scottish Terriers (Scottie, n = 1,363), and Shetland Sheepdogs (sheltie, n = 4,279). Significant increase in prevalence of the trait was seen in scotties and shelties during this period. In 1988, 73% of Dobermans, 30% of Scotties, and 28% of shelties tested had abnormal vWF:Ag concentration (less than 50% vWF:Ag). We found significant differences between breeds with respect to age and vWF:Ag concentration of clinically affected dogs at time of diagnosis. The affected Dobermans were older (Doberman mean age, 4.6 years; Scottie mean age, 1.7 years; sheltie mean age, 1.9 years) and had higher concentration of plasma vWF:Ag (doberman mean vWF:Ag, 15%; scottie mean vWF:Ag, 0%; sheltie mean vWF:Ag, 8%). Bleeding in affected dogs of all 3 breeds was observed predominantly from mucosal surfaces and from cutaneous sites of surgery or trauma. The most common site of mucosal bleeding in scotties and shelties was oral or nasal cavity, and in dobermans was the urogenital tract. Differences in clinical manifestations of vWD in purebred dogs may reflect heterogeneous defects within the vWF gene, causing a variety of abnormalities in production, structure, and function of vWF protein. Analogous to vWD in human beings, acquired deficiencies of vWF may also contribute to the clinical variability of vWD in dogs.

Wadsworth Center for Laboratories and Research, New York State Department of Health, Albany 12201-0509.

Raymond SL, Jones DW, Brooks MB, Clinical and laboratory features of a severe form of von Willebrand disease in Shetland sheepdogs. J Am Vet Med Assoc. 1990; 197:1342-1246.


Ten clinically affected Shetland Sheepdogs were evaluated to define their severe bleeding diathesis and were determined to have von Willebrand factor antigen (vWF:Ag) values less than 0.1% by ELISA assay. The virtual absence of vWF protein by ELISA assay and on multimeric analysis was diagnostic of either homozygosity or probable double heterozygosity for the canine von Willebrand disease (vWD) gene. Clinically affected dogs have type-III vWD and are the offspring of 2 heterozygous parents carrying type-I vWD. Twenty-three percent (1,428 dogs) of the more than 6,000 Shetland Sheepdogs screened for vWD at our facility since 1982 tested within the heterozygous carrier range for the common type-I form of this inherited disorder. Veterinarians and breeders should be aware of the potential for bleeding associated with elective and medical procedures in Shetland Sheepdogs and should use caution when breeding carriers of vWD because of the risk of producing clinically affected offspring with severe type-III vWD.

Wadsworth Center for Laboratories & Research, New York State Department of Health, Albany 12201-0509


• Oral tumors

Yoshida K, Yanail T, Iwasaki T, et al. Proliferative potential of canine oral epulides and malignant neoplasms assessed by bromodeoxyuridine labeling. Vet Path. 1999; 36:35-41.


The proliferative potential of canine oral lesions, including epulides, squamous cell carcinomas, a malignant melanoma, and a fibrosarcoma, was examined using a monoclonal antibody to bromodeoxyuridine (BrdU). Twenty-three dogs with oral masses were administered BrdU intravenously at a dose of 8 mg/kg 1 hour before surgery, and the BrdU labeling index (LI) of each lesion was determined immunohistochemically. The average BrdU LIs for the main proliferating elements in the fibromatous epulis (4 cases), ossifying epulis (2 cases), and acanthomatous epulis (10 cases) were 4.9, 3.0, and 8.8%, respectively. The squamous cell carcinomas (5 cases) had an average LI of 15.9%, and the LIs of the malignant melanoma and fibrosarcoma were 7.5 and 10.3%, respectively. All cases of acanthomatous epulides and squamous cell carcinoma treated with simple marginal surgical resection recurred within a short time. The higher LIs in the acanthomatous epulides, squamous cell carcinomas, and fibrosarcoma correlate well with their poor prognoses, reflected by rapid growth and frequent recurrence. Acanthomatous epulis is clearly distinguished from other epulides by its aggressive clinical behavior and high proliferative potential, which is equivalent to that of malignant tumors, despite a lack of cell atypia. The BrdU LI is a useful marker for evaluating the proliferative potential and prognosis of canine oral tumors.
Comment: Table 1 includes 7 Shetland Sheepdogs, 5 with acanthomatous epilus, 1 with ossifying epilus, and 1 with squamous cell carcinoma. The Shelties were between 10 and 13 years old.

Division of Comparative Pathology, New England Regional Primate Research Center, Harvard Medical School, One Pine Hill Drive, PO Box 9102, Southborough, MA 01772 (USA).

• Testicular tumors

Nodtvedt A, Gamlem H, Gunnes G, et al. Breed differences in the proportional morbidity of testicular tumours and distribution of histopathologic types in a population-based canine cancer registry. Vet Comp Oncol, 2011;9:45-54.


Histologically verified tumours submitted to the Norwegian Canine Cancer Register from 1990 to 1998 were studied (n = 14 401). The proportion of testicular tumours (n = 345) was 2.4%, and the breakdown of histological tumour diagnoses is presented. The frequency of the most common histopathological types was 33% interstitial (Leydig), 26.4% Sertoli and 33.9% seminomas/germ cell tumours. The average age at diagnosis was 10 years, but was significantly lower for Sertoli cell tumours (8.6 years) than for the other tumour types. Following a histopathological re-evaluation, 22.5% of the original tumor diagnoses were modified. Proportional morbidity ratios were calculated and individuals from the breeds Shetland sheepdog and Collie were five times more likely to have testicular tumours than the overall average for the registry. Breed differences in the distribution of histopathologic types were observed. Shetland sheepdog and Collie were most commonly diagnosed with Sertoli cell tumours, while all tumours from Norwegian elkhound in this material were seminomas.

Norwegian Sch Vet Sci, Dept Compan Anim Clin Sci, Oslo, Norway.


• Patent ductus arteriosus

Ackerman N, Burk R, Hahn AW, et al. Patent ductus arteriosus in the dog: a retrospective study of radiographic, epidemiologic, and clinical findings. Am J Vet Res, 1978; 39: 1805-1810.

Twenty-seven cases of patent ductus arteriosus (PDA) in the dog, which were confirmed by cardiac catheterization, surgical exploration, or at necropsy, were reviewed. A machinery murmur, electrocardiographic evidence of left ventricular enlargement, and radiographic evidence of cardiomegaly with an aortic and a pulmonary artery dilatation were consistent features. Surgical repair was successful in 65% of the dogs. The postoperative radiographic and electrocardiographic changes are described. A concomitant congenital defect was present in 2 dogs. The epidemiologic features of 532 dogs identified as having PDA and submitted to the National Cancer Institute's Veterinary Medical Data Program were reviewed. Miniature and Toy Poodles, Pomeranians, and Shetland Sheepdogs were identified as being at high risk for PDA. An excess of females over males was noticed.

U.S. based study

Dental disorders

• Caudal crossbite

Brine EJ. Endodontic disease of the mandibular first molar tooth secondary to caudal crossbite in a young Shetland sheepdog. J Vet Dent, 1999; 16:15-18.
A six month-old intact female Shetland sheepdog was referred to the University of Illinois Veterinary Dental Clinic with a left-sided mandibular deviation and a thickened left ventral mandible in the region of the first molar tooth. On oral examination, left caudal crossbite was diagnosed. Dental radiographs revealed endodontic disease of the mandibular first molar tooth involved in the crossbite. Because of the difficulty of treating caudal crossbite and the potential of a pathological mandibular fracture, the endodontically affected tooth was extracted. Ten months following the extraction, mandibular deviation and alveolar bone lysis were resolved, but alveolar ridge resorption was present. The abnormal occlusal relationship caused by the caudal crossbite may have led to movement of the tooth, resorption of the tooth alveolus, and irreversible pulpal damage. Although not employed in this case, use of alveolar ridge preservation techniques can prevent mandibular bone loss after extractions.

• Lance canine teeth

Ackerman LJ. The Genetic Connection: A Guide to Health Problems in Purebred Dogs, American Animal Hospital Association; 2011, page 41.
Lance canines mostly in: Shelties, Shiba Inu

DuPont GA, DeBowes LJ. Atlas of Dental Radiography in Dogs and Cats, Elsevier Health Sciences, 2008; pg 9-22.
Lance canine teeth in Shelties, Dachshunds, and cats – figs 9-20 and 9-21, page 9-22

Legendre L, Stepanik K. Correction of Maxillary Canine Tooth Mesioversion in Dogs. J Vet Dent:2008;25;216-221.
Predominately affects Shetland Sheepdogs. A few other breeds such as Italian greyhounds, miniature schnauzers, fox terriers, and some cats can have this condition.

Harvey CE.and PeterE P. Small animal dentistry, Mosby, 1993, pg 273
Lance canine teeth seen in Shelties, Scotties.

Endocrine Disorders

• Thyroid

Kennedy LJ, Quarmby S, Happ GM, et al. Association of canine hypothyroidism with a common major histocompatibility complex DLA class II allele. Tissue Antigens, 2006; 68: 82-86.

Dogs exhibit a range of immune-mediated conditions including a lymphocytic thyroiditis which has many similarities to Hashimoto's thyroiditis in man. We have recently reported an association in Doberman Pinschers between canine hypothyroidism and a rare DLA class II haplotype that contains the DLA-DQA1*00101 allele. We now report a further series of 173 hypothyroid dogs in a range of breeds where a significant association with DLA-DQA1*00101 is shown. (Includes 2 hypothyroid Shetland Sheepdogs.)

Centre for Integrated Genomic Medical Research, University of Manchester, Oxford Road, Manchester M13 9PT, UK.

Liver/Gallbladder Disorders

• Galbladder mucoceles

DeMonaco SM, Grant DC, Larson MM, et al. Spontaneous Course of Biliary Sludge Over 12 Months in Dogs with Ultrasonographically Identified Biliary Sludge. Journal of Veterinary Internal Medicine, 2016; 30:771-778.
This study was performed at the Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA.

Background: Biliary sludge is associated with gallbladder (GB) dysmotility and mucus hypersecretion suggesting a link between biliary sludge and the formation of GB mucoceles (GBM). If biliary sludge progresses to GBM, treatment to reduce the production and progression of sludge is warranted.

Hypothesis/Objectives: The objective of this study was to determine the course of biliary sludge in dogs.

Animals: Seventy-seven healthy, client-owned dogs ≥4 years of age screened for biliary sludge; 45 affected dogs identified.

Methods: Prospective, observational design. Serial ultrasound examinations were evaluated at 3, 6, 9, and 12 months to monitor degree of sludge based on proportion of GB filled with sludge (mild [0.01–24.4%], moderate [24.5–49.4%], moderate to severe [49.5–74.4%], severe [74.5–100%]), gravity dependency of sludge, and GB dimensions.

Results: After 1 year of follow-up, the degree of sludge was mild (34%), moderate (47%), moderate to severe (13%), severe (3%), or absent (3%). There was no significant difference in median degree of sludge over 1 year (P = .36). There were no significant changes in the gravity dependency of sludge over 1 year. A subset of dogs, 24%, with initial gravity-dependent sludge developed a combination of nondependent and dependent sludge. Dogs had resolved (2%), decreased (19%), static (40%), increased (29%), or recurrent (10%) sludge at the conclusion of the study.

Conclusions and Clinical Importance: Biliary sludge was prevalent, affected dogs remained asymptomatic, and it rarely resolves in healthy dogs over a period of 1 year. Some dogs developed nongravity-dependent sludge within 1 year, which might indicate changes in consistency of sludge.

Gookin JL, Correa MT, Peters A, et al. Association of Gallbladder Mucocele Histologic Diagnosis with Selected Drug Use in Dogs: A Matched Case-Control Study. Journal of Veterinary Internal Medicine, 2015; 29: 1464–1472. doi: 10.1111/jvim.13649.

The study was conducted at the College of Veterinary Medicine, North Carolina State University, 1060 William Moore Drive, Raleigh, NC 20607.

Keywords: Bile; Canine; Mucus; Xenobiotic
Background: The cause of gallbladder mucocele (GBM) formation in dogs currently is unknown. Many available drugs represent a newer generation of xenobiotics that may predispose dogs to GBM formation.
Objective: To determine if there is an association between the histologic diagnosis of GBM in dogs and administration of selected drugs.
Animals: Eighty-one dogs with a histologic diagnosis of GBM and 162 breed, age, and admission date-matched control dogs from a single referral institution.
Methods: Medical records of dogs with GBM and control dogs from 2001 to 2011 were reviewed. Owner verification of drug history was sought by a standard questionnaire. Reported use of heartworm, flea, and tick preventatives as well as nonsteroidal anti-inflammatory drugs, analgesics, corticosteroids, or medications for treatment of osteoarthritis was recorded.
Results: Dogs with GBM were 2.2 times as likely to have had reported use of thyroxine (as a proxy for the diagnosis of hypothyroidism) as control dogs (95% confidence interval [CI], 0.949–5.051), 3.6 times as likely to have had reported treatment for Cushing's disease (95% CI, 1.228–10.612), and 2.3 times as likely to have had reported use of products containing imidacloprid (95% CI, 1.094–4.723). Analysis of a data subset containing only Shetland sheepdogs (23 GBM and 46 control) indicated that Shetland sheepdogs with GBM formation were 9.3 times as likely to have had reported use of imidacloprid as were control Shetland sheepdogs (95% CI, 1.103–78.239).
Conclusions and Clinical Importance: This study provides evidence for an association between selected drug use and GBM formation in dogs. A larger epidemiologic study of Shetland sheepdogs with GBM formation and exposure to imidacloprid is warranted.

Guess SC, Harkin KR, Biller DS: Anicteric gallbladder rupture in dogs: 5 cases (2007–2013). J Am Vet Med Assoc. 2015; 247:1412–1414. doi: 10.2460/javma.247.12.1412
Take home points:
• 5 dogs were affected, only one was a Shetland Sheepdog.
• Gallbladder rupture was thought to be secondary to gallbladder mucoceles.
• Bloodwork did not identify a gallbladder problem.
• Free abdominal fluid was identified via ultrasound evaluation in all dogs.
• Evaluation of free abdominal fluid for bile acids may be needed to confirm gallbladder rupture.
• Gallbladder rupture is a surgical emergency.
Excerpts from the article are presented below.
“Results –
…….Five dogs met the criteria for study inclusion (2 spayed females and 3 castrated males). The breeds included mixed (n = 2), Pomeranian (1), Shetland Sheepdog (1), and Bichon Frise (1). Mean age at the time of diagnosis was 10 years (median, 10 years; range, 8 to 12 years). Mean and median body weights were 15.3 and 14 kg (33.7 and 30.8 lb.), respectively…..
Discussion -
This retrospective case series included 5 dogs with gallbladder rupture, mild to moderate abdominal effusion, and serum total bilirubin concentrations within reference limits. All dogs described in this report had free abdominal fluid detected during an ultrasonographic examination and surgically confirmed gallbladder rupture. Although hyperbilirubinemia is typically considered a key part of the diagnosis in patients with biliary disease,5 results of this case series show that patients can have a ruptured gallbladder without evidence of icterus, with serum total bilirubin concentrations within reference limits, and with unremarkable peritoneal fluid bilirubin concentration (< 2 times the concentration in serum)………
The findings of this case series suggested that hyperbilirubinemia and high concentrations of bilirubin in abdominal fluid contents are not necessarily present in dogs with gallbladder rupture. Furthermore, our results suggested that testing of abdominal fluid for bile acids may be indicated in some cases in which a diagnosis remains challenging or elusive. Additional studies are needed to further evaluate the diagnostic value of abdominal fluid bile acids measurement prospectively in a larger number of patients….
Four of the 5 dogs described in the present report had evidence of gallbladder necrosis, and 1 dog had evidence of fibrinolytic, suppurative cholecystitis on histologic evaluation. Although the number of dogs in this study was extremely small, on the basis of histopathologic findings in these cases, pressure necrosis secondary to gallbladder mucocele presence is considered a possible mechanism for gallbladder rupture, and this hypothesis has been described previously.4,7,8 Because the prevalence of gallbladder mucocele is reportedly increasing in canine patients, further exploration into the pathogenesis of mucoceles and gallbladder rupture without bile duct obstruction is needed in veterinary medicine.2,4,8,12 …”

Kesimer M, Cullen J, Cao R, Radicioni G, et al. Excess Secretion of Gel-Forming Mucins and Associated Innate Defense Proteins with Defective Mucin Un-Packaging Underpin Gallbladder Mucocele Formation in Dogs. PLoS ONE; 2015; 10(9): e0138988. doi:10.1371/journal.pone.0138988,
Mucosal protection of the gallbladder is vital yet we know very little about the mechanisms involved. In domestic dogs, an emergent syndrome referred to as gallbladder mucocele formation is characterized by excessive secretion of abnormal mucus that results in obstruction and rupture of the gallbladder. The cause of gallbladder mucocele formation is unknown. In these first mechanistic studies of this disease, we investigated normal and mucocele-forming dog gallbladders to determine the source, identity, biophysical properties, and protein associates of the culprit mucins with aim to identify causes for abnormal mucus behavior. We established that mucocele formation involves an adoptive excess secretion of gel forming mucins with abnormal properties by the gallbladder epithelium. The mucus is characterized by a disproportionally significant increase in Muc5ac relative to Muc5b, defective mucin un-packaging, and mucin-interacting innate defense proteins that are capable of dramatically altering the physical and functional properties of mucus. These findings provide an explanation for abnormal mucus behavior and based on similarity to mucus observed in the airways of people with cystic fibrosis, suggest that abnormal mechanisms for maintenance of gallbladder epithelial hydration may be an instigating factor for mucocele formation in dogs.
The underlying cause of gallbladder mucocele formation in the dog is currently somewhat of a mystery. Several predisposing factors such as breed predisposition [11, 15], concurrent endocrinopathies [13], and hyperlipidemia [11, 15] suggest both a genetic and hormonal/metabolic contribution to disease pathogenesis. However, the breeds of dog affected and endocrinopathies commonly associated with gallbladder mucocele formation have existed long before emergence of the disease as a clinical entity and are not found in all dogs diagnosed with the disease. Accordingly, these are unlikely to be a direct cause, but rather an exacerbating factor to disease pathogenesis. Efforts to link a genetic defect in ABCB4, a hepatocyte canicular membrane phosphatidylcholine flippase, in the Shetland sheepdog was initially promising but later disproven [24]. A theory that poor gallbladder motility [16] causes gallbladder mucocele formation is difficult to prove once the gallbladder is filled with mucus and gallbladder paresis does not result in mucocele formation in people. The disease is not a consequence of common bile duct obstruction [25], however mucus can eventually extend into and obstruct hepatic bile drainage. Increased mucin secretion can be caused by bacterial cholecystitis; however infection of the gallbladder is an inconsistent finding in dogs with gallbladder mucocele formation [9–12, 14]. Despite many descriptions of proliferative changes in the gallbladder epithelium [26], there exist no diseases of the gallbladder in people that closely mirror the histological appearance of gallbladder mucocele formation in dogs. The only descriptions of gallbladder mucosa that are similar to gallbladder mucocele formation are in animals experimentally treated with progestins [27–29] or lacking functional cystic fibrosis transmembrane regulatory (CFTR) protein expression[30,31]. Alas, the specific mechanisms underpinning the initiating event of the disease pathogenesis in dogs has remained elusive. …… MORE…….

Cullen JM, Willson CJ, Minch, JD, Kimbrough CL, Mealey KL. Lack of association of ABCB4 insertion mutation with gallbladder mucoceles in dogs. Journal of Veterinary Diagnostic Investigation, 2014; 26:434-436.
The etiology of canine gallbladder mucocele (GBM) has not yet been identified. However, several studies have linked GBM in dogs to particular breeds (Shetland Sheepdogs are commonly implicated), concurrent endocrine disease (hyperadrenocorticism and/or hypothyroidism), and a mutation in the canine ABCB4 gene (ABCB4 1583_1584G), particularly in Shetland Sheepdogs. The current study assessed ABCB4 1583_1584G, in a wider sample of dogs with GBM compared with age and breed-matched controls. ABCB4 1583_1584G was identified in 4 of 8 Shetland Sheepdogs and 13 of 28 other breeds with GBM. ABCB4 1583_1584G was also detected in 9 of 12 Shetland Sheepdogs and 23 of 37 other breeds that did not have GBM. No statistically significant association existed between ABCB4 1583_1584G and the presence of GBM for all dogs combined or for Shetland Sheepdogs alone. In contrast to previously reported findings, the current study did not identify a strong association between ABCB4 1583_1584G and GBM in Shetland Sheepdogs or other breeds.

Malek S, Sinclair E, Hosgood, G, Moens, et al. Clinical Findings and Prognostic Factors for Dogs Undergoing Cholecystectomy for Gall Bladder Mucocele. Veterinary Surgery, 2013; 42: 418–426. doi: 10.1111/j.1532-950X.2012.01072.x
Diagnosis of gallbladder mucoceles was confirmed by histopathology and 74% were diagnosed based on preoperative abdominal ultrasonography. Intraoperative evidence of gall bladder rupture was noted in 10 dogs (23%), and 16 (37%) had evidence of previous leakage in the abdominal cavity. One dog had positive bacterial growth from the gall bladder content. The most common histopathologic findings in liver biopsies obtained at surgery were cholangiohepatitis, biliary hyperplasia, or cholestasis. Univariate analysis showed evidence of postoperative hypotension (P = .05) to be significantly negatively associated with survival. Significant difference in mean postoperative serum lactate (P = .034) and postoperative packed cell volume (P = .063) between dogs that survived and died was also noted.

Elevations in postoperative serum lactate concentrations and immediate postoperative hypotension in dogs undergoing cholecystectomy for gall bladder mucoceles are associated with poor clinical outcome.

5 of the dogs in the above study were Shetland Sheepdogs.

Tsukagoshi T, Ohno K, Tsukamoto A, Decreased gallbladder emptying in dogs with biliary sludge or gallbladder mucocele. Vet Radiol & Ultrasound. 2012; 53:84-91.
Biliary sludge in dogs is dismissed commonly as an incidental finding. On the other hand, gallbladder mucocele is reported increasingly in dogs and can lead to biliary obstruction or gallbladder rupture. Cholestasis is suspected to play a role in development of sludge and mucoceles, though there are no data in dogs to support this. We investigated gallbladder emptying, a key factor in biliary flow, in dogs with mobile sludge, immobile sludge, or gallbladder mucocele and in healthy controls. Gallbladder ejection fraction estimated by ultrasonography was used as the index of gallbladder emptying. The ejection fraction at 60 min after eating was significantly decreased in all three abnormal groups. Moreover, all dogs with sludge or a mucocele had gallbladder distension. These changes were the greatest in the mucocele group. Thus, biliary stasis occurs not only in dogs with gallbladder mucocele but also in dogs with biliary sludge. Cholestasis may play a role in the pathogenesis or progression of these diseases in dogs.
Comment: Two of 7 dogs with mucoceles were Shetland Sheepdogs.
University of Tokyo, Tokyo, Japan.

Mealey KL, Minch JD, White SN, et al: An insertion mutation in ABCB4 is associated with gallbladder mucocele formation in dogs. Comp Hepatol, 2010; 9:6.
ABCB4 functions as a phosphatidylcholine translocater, flipping phosphatidylcholine across hepatocyte canalicular membranes into biliary canaliculi. In people, ABCB4 gene mutations are associated with several disease syndromes including intrahepatic cholestasis of pregnancy, progressive familial intrahepatic cholestasis (type 3), primary biliary cirrhosis, and cholelithiasis. Hepatobiliary disease, specifically gallbladder mucocele formation, has been recognized with increased frequency in dogs during the past decade. Because Shetland Sheepdogs are considered to be predisposed to gallbladder mucoceles, we initially investigated ABCB4 as a candidate gene for gallbladder mucocele formation in that breed, but included affected dogs of other breeds as well.
An insertion (G) mutation in exon 12 of canine ABCB4 (ABCB4 1583_1584G) was found to be significantly associated with hepatobiliary disease in Shetland Sheepdogs specifically (P < 0.0001) as well as other breeds (P < 0.0006). ABCB4 1583_1584G results in a frame shift generating four stop codons that prematurely terminate ABCB4 protein synthesis within exon 12, abolishing over half of the protein including critical ATP and a putative substrate binding site.
The finding of a significant association of ABCB4 1583_1584G with gallbladder mucoceles in dogs suggests that this phospholipid flippase may play a role in the pathophysiology of this disorder. Affected dogs may provide a useful model for identifying novel treatment strategies for ABCB4-associated hepatobiliary disease in people.
Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA

Mayhew PD, Mehler SJ, Radhakrishnan A. Laparoscopic Cholecystectomy for Management of Uncomplicated Gall Bladder Mucocele in Six Dogs. Vet Surg, 2008; 37: 625-630.
Comment: One of the dogs in the report was a Shetland Sheepdog.

Aguirre AL, Center SA, Randolph JF, et al. Gallbladder disease in Shetland Sheepdogs: 38 cases (1995-2005), J Am Vet Med Assoc, 2007; 231:79-88.
Objective—To determine risk, clinical features, and treatment responses for gallbladder disorders in Shetland Sheepdogs.
Design—Retrospective case-control study.
Animals—38 Shetland Sheepdogs with gallbladder disease.
Procedures—Medical records were reviewed for signalment, history, physical findings, laboratory results, imaging features, coexistent illnesses, histologic findings, treatments, and survival rates.
Results—Mature dogs with gastrointestinal signs were predisposed (odds ratio, 7.2) to gallbladder disorders. Gallbladder mucocele was confirmed in 25 dogs. Concurrent problems included pancreatitis, hyperlipidemia, corticosteroid excess, hypothyroidism, protein-losing nephropathy, diabetes mellitus, cholelithiasis, and gallbladder dysmotility. Mortality rate was 68% with and 32% without bile peritonitis. Nonsurvivors had high WBC and neutrophil count and low potassium concentration. Although preprandial hypercholesterolemia, hypertriglyceridemia, and high serum liver enzyme activities were common, gallbladder disease was serendipitously discovered in 11 of 38 dogs. Histologic examination (n = 20 dogs) revealed gallbladder cystic mucosal hyperplasia in 20 dogs, cholecystitis in 16, periportal hepatitis in 9, and vacuolar hepatopathy in 7. Surgery included cholecystectomy (n = 17) and cholecystoenterostomy (4). In 1 hyperlipidemic dog without clinical signs, gallbladder mucocele resolved 6 months after beginning use of a fat-restricted diet and ursodeoxycholic acid.
Conclusions and Clinical Relevance—Shetland Sheepdogs are predisposed to gallbladder disorders, with mucoceles and concurrent dyslipidemia or dysmotility in many affected dogs. Most dogs were without clinical signs during mucocele development. Low survival rate after cholecystectomy in clinically affected dogs suggested that preemptive surgical interventions may be a more appropriate treatment strategy.
Departments of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY

Worley DR, Hottinger HA, Lawrence HJ. Surgical management of gallbladder mucoceles in dogs: 22 cases (1999–2003). J Am Vet Med Assoc, 2004; 225:1418–1422.
Animals—22 client-owned dogs. (Includes 4 Shetland Sheepdogs)
Procedures—Medical records of dogs with gallbladder mucoceles that were treated surgically were reviewed. History, clinical signs, results of selected clinicopathologic analyses and abdominal ultrasonography, surgical procedure performed, results of histologic examination of a liver biopsy specimen, and survival time were recorded. Followup information was obtained via telephone interview with owners and referring veterinarians.
Results—Dogs were 7 to 15 years of age and had nonspecific clinical signs (vomiting, anorexia, and lethargy). Physical examination findings included icterus, signs of depression, and signs of discomfort on palpation of the abdomen . Sixteen dogs had a definitive diagnosis and 6 dogs were strongly suspected of having a gallbladder mucocele on the basis of results of abdominal ultrasonography. Fifteen dogs survived after surgery; 3 of these dogs had bile-induced peritonitis, and 4 had pancreatitis. One dog was euthanatized as a result of severe pancreatitis, and 1 was euthanatized because of acute renal failure; 5 dogs died as a result of pancreatitis, cholecystitis, or bile-induced peritonitis. Hepatic abnormalities were detected histologically in all dogs.
Conclusions and Clinical Relevance—No predictors of survival were identified. No associations between outcome of surgical treatment (survival vs nonsurvival) and preoperative findings, biliary rupture, surgical procedure performed, results of histologic examination of the liver, or development of pancreatitis were found. Cholecystoduodenostomy and cholecystectomy appear to be acceptable treatments for gallbladder mucocele.
Gulf Coast Veterinary Surgery, Houston, TX

• Portosystemic shunts

Tobias KM, Rohrbach BW. Association of breed with the diagnosis of congenital portosystemic shunts in dogs: 2,400 cases (1980–2002). J Am Vet Med Assoc, 2003; 223:1636-1639.
Objective—To determine the annual and overall proportion of diagnoses of congenital portosystemic shunts (CPSS) in dogs and identify breeds at increased risk for CPSS.
Design—Retrospective study.
Animals—2,400 dogs with CPSS from veterinary teaching hospitals that reported to the Veterinary Medical Database (VMDB) from January 1, 1980 to February 28, 2002.
Procedure—The proportion of diagnoses of CPSS was calculated for all dogs and each breed recorded in the VMDB annually and for the 22.2-year period. Odds ratios and adjusted confidence intervals were calculated for breeds with at least 100 accessions by comparing odds of each breed with a diagnosis of CPSS with that of mixed-breed dogs.
Results—Congenital portosystemic shunts were reported in 0.18% of all dogs and 0.05% of mixed breed dogs. The proportion of diagnoses of CPSS increased from 5 in 10,000 dogs in 1980 to 5 in 1,000 dogs in 2001. Yorkshire Terriers had the greatest total number of diagnoses of CPSS. Thirty-three breeds were significantly more likely to have a diagnosis of CPSS, compared with mixed-breed dogs. The greatest proportions of diagnoses were found in Havanese (3.2%), Yorkshire Terriers (2.9%), Maltese (1.6%), Dandie Dinmont Terriers (1.6%), and Pugs (1.3%).
Conclusions and Clinical Relevance—Certain breeds appear to be at increased risk for CPSS, compared with mixed-breed dogs. The increased odds ratios among specific breeds support the hypothesis of a genetic predisposition for CPSS. Clients and veterinarians should consider appropriate diagnostic tests for dogs with clinical signs and those used for breeding from breeds with increased risk of CPSS. (J Am Vet Med Assoc 2003;223:1636–1639)
Comment: 59 Shetland Sheepdogs were included in the report and represented 0.26% of affected dogs. They were one of the 33 breeds more likely to have a diagnosis of CPSS compared to mixed-breed dogs with an increased risk of 5.2. Havanese has the greatest increased risk of 64.9 times that of mixed breed dogs. Mixed-breed dogs with CPSS represented 0.05% of affected dogs.
Departments of Small Animal Clinical Sciences and Large Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996.

• Liver - other

Hall-Fonte DL, Center SA, McDonough SP, et al. Hepatocutaneous syndrome in Shih Tzus: 31 cases (1996–2014). J Am Vet Med Assoc, 2016; 248: 802-813.

Results suggested that HCS may have a heritable component in Shih Tzus, although the condition may also be identified in Shih Tzus without affected relatives. .. Previous reports have suggested that HCS is more common in male than female dogs, with a median age of onset of 10 years and a predilection for medium- and small-sized dogs. In a review, 4 of 110 cases, mixed-breed dogs were most common (28%), with breeds represented by ≥ 10 dogs including Shetland Sheepdog, Cocker Spaniel, and West Highland White Terrier. Reportedly, affected dogs are typically examined because of painful cutaneous lesions, lethargy, inappetence, and weight loss, and common clinicopathologic abnormalities include nonregenerative anemia and high hepatic enzyme activities (especially, high ALP activity).

Neurological and/or Muscular Disorders

• Degenerative myelopathy

Zeng R, Coates JR, Johnson CG, et al.: Breed distribution of SOD1 alleles previously associated with canine degenerative myelopathy. J Vet Internal Med, 2014; 28:515-521.

• Epilepsy

Hülsmeyer V-I, Fischer A, Mandigers PJJ, et al. International Veterinary Epilepsy Task Force’s current understanding of idiopathic epilepsy of genetic or suspected genetic origin in purebred dogs. BMC Veterinary Research. 2015; 11:175. doi:10.1186/s12917-015-0463-0.


Canine idiopathic epilepsy is a common neurological disease affecting both purebred and crossbred dogs. Various breed-specific cohort, epidemiological and genetic studies have been conducted to date, which all improved our knowledge and general understanding of canine idiopathic epilepsy, and in particular our knowledge of those breeds studied. However, these studies also frequently revealed differences between the investigated breeds with respect to clinical features, inheritance and prevalence rates. Awareness and observation of breed-specific differences is important for successful management of the dog with epilepsy in everyday clinical practice and furthermore may promote canine epilepsy research. The following manuscript reviews the evidence available for breeds which have been identified as being predisposed to idiopathic epilepsy with a proven or suspected genetic background, and highlights different breed specific clinical features (e.g. age at onset, sex, seizure type), treatment response, prevalence rates and proposed inheritance reported in the literature. In addition, certain breed-specific diseases that may act as potential differentials for idiopathic epilepsy are highlighted.

Keywords: Idiopathic epilepsy, Dog, Breed, Epilepsy prevalence, Epileptic seizure

Below is a section from this article regarding Shelties. This is a pretty good article.

Shetland Sheepdog
Three reports about epilepsy in Shetland Sheepdogs are available in the current literature [109–111]. All studies were conducted in Japan. The first study was published in 2002 and reports about a large family of Shetland Sheepdogs with natural occurring familial frontal lobe epilepsy defined by EEG analysis and seizure semiology [109]. Two litters of one large family were produced deliberately for prospective examination in this study. A detailed definition for idiopathic epilepsy was not provided [109]. The age at seizure onset was predominantly between 1 and 1.5 years of age. The average seizure frequency varied from one seizure every week to one every 6 months. The gender distribution was 79 % females compared to 21 % males. The seizure type was predominantly defined as generalised in almost all cases, but detailed classification of initial seizures signs was not conducted [109], hence a proportion of dogs might have experienced focal seizures evolving into generalised seizures instead of (primary) generalised seizures. EEG examination identified paroxysmal discharges predominantly in the frontal lobes [109]. Based on this, this epilepsy was postulated as familial frontal lobe epilepsy, however with prolonged disease duration also the parietal, temporal and occipital lobes showed epileptiform activity on EEG [109]. Pedigree analysis excluded potential mitochondrial or sex-linked inheritance and a multifactorial inheritance was suggested to be most likely [109]. Identification of a causative gene mutation has not yet reported. Additional findings of the latter study were increased aspartate and glutamate levels in the CSF in some of the epileptic dogs compared to control dogs [109]. Hence, another study that was published in 2005 focused on intracerebral microdialysis and EEG recording as well as histopathological examination of epileptic Shetland Sheepdogs [110]. Intracerebral microdialysis and EEG – both conducted during hyperventilation – revealed increased extracellular glutamate and aspartate concentrations in the cerebral cortex of epileptic dogs. Coinciding with the increase in excitatory neurotransmitters, an increase in paroxysmal discharges on EEG was detected. On histopathological examination, dogs affected by status epilepticus showed a reduced density of glutamate receptors in the area of the lateral nucleus of the thalamus. In addition, glutamate positive granules were found within the perineural spaces of the cerebral cortex. It was considered possible that a decrease of glutamate receptor levels may induce an increase in extracellular glutamate concentration, which would evoke neuronal hyperexcitability and may contribute to a collapse of extracellular glutamate regulation during status epilepticus [110]. Another case report of a Shetland sheepdog with drug resistant epilepsy identified hippocampal and mesial temporal lobe sclerosis on necropsy. However, this finding was suggested as a secondary phenomenon induced by recurrent seizures rather than to be a primary seizure-causing finding [111]. Potential breed-specific diseases that may mimic idiopathic epilepsy: For the Shetland sheepdog a spongiform encephalopathy has been reported, which appears with neurological signs that may mimic a seizure event. However, clinical manifestation is early within the first weeks of life (between the 2– 9 weeks of life) and consists of tremors, ataxia, paresis, spasticity and loss of cranial nerve function. DNA sequencing of affected puppies showed a point mutation that resulted in an amino acid change of mitochondrial encoded cytochrome b [112]. The Shetland sheepdog is also a dog breed frequently affected by ABCB1/MDR1-gene mutation, with identified mutant allele frequencies between 1 − 12 % depending on the respective study and geographic area [33], which may need to be considered in Shetland sheepdogs with acute seizures and potential previous exposure to neurotoxic P-gp substrates.

Morita T, Takahashi M, Takeuchi T, et al. Changes in extracellular neurotransmitters in the cerebrum of familial idiopathic epileptic Shetland sheepdogs using an intracerebral microdialysis technique and immunohistochemical study for glutamate metabolism. J Vet Med Sci, 2005;67:1119-1126.

Intracerebral microdialysis combined with electroencephalographic recordings was performed on 4 dogs of a familial idiopathic epileptic Shetland sheepdog colony to identify the kinds of neurotransmitters responsible for seizure activity. Immunohistochemistry using glutamate (Glu), glutamate transporter (GLT-1 and GLAST), and glutamine synthetase (GS) antibodies was also carried out on the cerebrum of four familial dogs that died of status epilepticus (SE). High values for extracellular levels of Glu and aspartate (ASP) were detected in association with an increased number of spikes and sharp waves during hyperventilation in 3 of 4 the familial epileptic dogs. The values of other amino acids analyzed were not altered in any of the familial epileptic dogs. Immunohistochemically, Glu-positive granules were occasionally found in the perineuronal spaces of the cerebral cortex in 3 of the familial epileptic dogs that died of SE. Immunostains for GLT-1 antibody predominantly decreased in the cerebral cortex and lateral nucleus of the thalamus in all the dogs that died of SE, whereas there were no differences detected in immunolabellings for GLAST and GS antibodies between familial epileptic dogs and controls. These results suggest that an extracellular release of both Glu and Asp may play an important role in the occurrence of seizure activity in this epileptic colony, and that a decreased expression of astrocytic GLT-1 may be related to development of SE.

Department of Veterinary Pathology, Tottori University, Japan.

Comment: In the above article, they had a colony of Shelties with epilepsy. Four of them that died of status epilepticus (would not stop seizing) ranged in age from 8 mos. to 4 yrs.

Hasegawa D, Fujita M, Nakamura S, et al.: Electrocorticographic and histological findings in a Shetland sheepdog with intractable epilepsy. J Vet Med Sci, 2002; 64:277-279.
A Shetland sheepdog with epilepsy refractory to antiepileptic drugs was brought to the division of Veterinary Radiology at Nippon Veterinary and Animal Science University. Scalp electroencephalography and computed tomography was performed, but no abnormality was detected in either examination. To obtain detailed information, electrodes were implanted on the dura mater, and the electrocorticogram (ECoG) was recorded. In the ECoG, sporadic spikes were detected in the left parietal region, suggesting the presence of the epileptic focus in this region. After the dog's death, abnormalities of gyri were found in the region where spikes were detected in the ECoG. On histopathological examination, laminar malacia of the cingulate gyrus was observed. Furthermore, in the hippocampus, neuronal loss of pyramidal cells was observed.
Division of Veterinary Radiology, Nippon Veterinary and Animal Science University, Musashinoshi, Tokyo, Japan.

Morita T, Shimada A,Takeuchi T, et al. Cliniconeuropathologic findings of familial frontal lobe epilepsy in Shetland sheepdogs. Can J Vet Res, 2002; 66:35-41.

We examined an epileptic focus by electroencephalography (EEG) by using an international 10-20 electrode system in 11 Shetland sheep dogs affected with familial idiopathic epilepsy. We also performed an evaluation of the amino acids in the cerebrospinal fluid (CSF) and a pathologic examination of the brains of 8 dogs that died from status epilepticus. Continuous electroencephalography demonstrated that an epileptic focus was initially detected in the frontal lobe, particularly the internal area, and that paroxysmal foci developed diffusely in other lobes of affected dogs with recurrent convulsions. The EEG analyses indicated spike and sharp wave complexes, which were considered to be paroxysmal discharges. An increased value for glutamate or aspartate was found in the CSF of some epileptic dogs. Histologically, acute neuronal necrosis and astrocytosis were distributed predominantly in the cingulate cortex and internal area of frontal cortex, less frequently in other areas of the cerebrum. The results of this study suggest that, initially, the dogs have an epileptic focus in the frontal lobe, and that the focus extends gradually to other areas of the cerebrum. Based on the distribution of neuronal necrosis and astrocytosis, acute neuronal damage may be related to the superexcitation of neurons following epilepsy.

Department of Veterinary Pathology, Tottori University, Tottori-shi, Japan.

• Multiple drug sensitivity syndrome (MDR-1 gene)

Deshpande D, Hill KE. Mealey KL, et al. The Effect of the canine ABCB1-1Δ mutation on sedation after intravenous administration of acepromazine. Journal of Veterinary Internal Medicine, 2016; 30:636-641. doi: 10.1111/jvim.13827

This is an open access article. Links to the entire article in different formats can be found at:

This study published in 2016 concerned the use of acepromazine (a commonly used tranquilizer and preanesthetic agent) in dogs having the ABCB1 (MDR-1) gene. The number of dogs in the study was 29 Collies - 10 mutant/mutant, 10 mutant/normal, and 9 normal/normal. The authors found that dogs homozygous for the mutation had increased depth and duration of sedation after acepromazine IV compared to normal dogs. They authors concluded that in "ABCB1 mut/mut dogs, acepromazine dose rates should be reduced and careful monitoring performed during sedation."
Bottom line, test your dogs and inform/educate your veterinarian about the risks of various drugs in dogs with the MDR-1 mutation. Gradually, try to breed away from it. The mutation is not nearly as common in Shelties as other herding breeds.

Geyer J, Döring B, Godoy JR, et al. Frequency of the nt230 (del4) MDR1 mutation in Collies and related dog breeds in Germany. J Vet Pharmacol Ther, 2005; 28:545-551.

MDR1 (ABCB1) P-glycoprotein exerts a protective function in the blood-brain barrier thereby limiting the entry of many drugs and other xenobiotics to the central nervous system. A nonsense mutation has been described for Collies and related dog breeds which abolishes this function and is associated with increased susceptibility to neurotoxic side effects of several drugs including ivermectin, moxidectin and loperamide. In order to evaluate the occurrence and frequency of this nt230 (del4) MDR1 mutation in Germany, we screened 1500 dogs. Frequency of the homozygous mutated genotype was highest for Collies (33.0%), followed by Australian Shepherd (6.9%) and Shetland Sheepdog (5.7%). Thirty-seven percent of the Wäller dogs and 12.5% of the Old English Sheepdogs were heterozygous for the mutant MDR1 (-) allele. Considering the predominant role of MDR1 P-glycoprotein in drug disposition and in particular for blood-brain barrier protection, MDR1 genotype-based breeding programs are recommended for improving the safety of drug therapy in these canine breeds.

Institute of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Justus-Liebig-University of Giessen, Giessen, Germany.

Kawabata A, Momoi Y, Inoue-Murayama M, et al. Canine mdr1 gene mutation in Japan. J Vet Med Sci, 2005; 67:1103-1107.

Frequency of the 4-bp deletion mutant in canine mdr1 gene was examined in 193 dogs of eight breeds in Japan. The mutant allele was found in Collies, Australian Shepherds, and Shetland Sheepdogs, where its respective frequencies were 58.3%, 33.3%, and 1.2%. The MDR1 protein was detected on peripheral blood mononuclear cells (PBMC) from a MDR1/MDR1 dog, but not on PBMC from a mdr1-1Delta/mdr1-1Delta Collie. Rhodamine 123 was extruded from MDR1/MDR1 lymphocytes. That excretion was inhibited by a MDR1 inhibitor, verapamil. On the other hand, Rh123 excretion was not observed from lymphocytes derived from a mdr1-1Delta/mdr1-1Delta Collie. These results indicated that the mutant mdr1 allele also existed in Collie-breed dogs in Japan at high rates and that mdr1-1Delta /mdr1-1Delta dogs have no functional MDR1.

Department of Veterinary Internal Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Japan.

• Neurology - Other

Heller HB, Steinberg H, Drees R, et al. What Is Your Neurologic Diagnosis? J Am Vet Med Assoc, 2016; 249:55-57.

Comment: 4-yr-old female Shetland Sheepdog with a history of acute onset of ataxia. Diagnosis: ependymal cyst. The dog survived nearly 3 years after diagnosis.

Ependymal cysts are reported rarely in the veterinary and human medical literature.1,2 In people, ependymal cysts arise most commonly from the lateral ventricle3 but have been reported in the fourth ventricle and cerebellopontine angle.4–8 In humans, ependymal cysts often have no associated clinical signs; however, when patients are affected clinically, the signs reflect supratentorial disease (eg, seizures or motor deficits) or infratentorial disease (eg, cranial nerve VII, VIII, or IX dysfunction).9 The dog of the present report had central vestibular (cranial nerve VIII) dysfunction initially, with cerebellar signs developing later. As for this dog, CSF abnormalities have been noted previously for a dog with an intracranial cyst and were considered to be secondary to leakage of cystic fluid or compression of surrounding tissues.10 The dog of the present report had a fair to good prognosis as evidenced by an almost 3-year survival period following diagnosis and intermittent administration of prednisone. Ependymal cysts are rare in dogs; however, an ependymal cyst should be considered a differential diagnosis for dogs with a cystic lesion at the level of the fourth ventricle.

Department of Medical Sciences, College of Veterinary Medicine, University of Wisconsin, Madison, WI 53706. (Barnes Heller, Petersen); Department of Pathobiological Sciences, College of Veterinary Medicine, University of Wisconsin, Madison, WI 53706. (Steinberg); Department of Surgical Sciences, College of Veterinary Medicine, University of Wisconsin, Madison, WI 53706. (Drees)

Li FY, Cuddon PA, Song J, et al. Canine spongiform leukoencephalomyelopathy is associated with a missense mutation in cytochrome b. Neurobiol Dis, 2006; 21:35-42.

Two families of dogs (Australian cattle dogs and Shetland sheepdogs) with an inherited "spongiform leukoencephalomyelopathy" were identified, with widespread vacuolation of white matter of the brain and spinal cord. Affected dogs of both breeds developed tremors at 2-9 weeks of age followed by progressive neurological worsening with ataxia, paresis, paralysis, spasticity, and cranial nerve dysfunction. The modes of inheritance of both families were most likely maternal. The cerebrospinal fluid (CSF) analysis showed elevated ratio of 3-OH butyrate to acetoacetic acid. Mitochondrial DNA sequencing showed a G to A transition at 14,474 nt (G14474A, GenBank accession no. NC002008 ) that results in an amino acid change of valine-98 to methionine (V98M) of mitochondrial encoded cytochrome b. Western blot analysis showed increased levels of core I and core II but decreased level of cytochrome c1 of the complex III and cytochrome c oxidase of the complex IV of the respiratory chain.

Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, 2015 Linden Drive, Madison, WI 53706, USA.

Wood SL, Patterson JS. Shetland Sheepdog Leukodystrophy. J Vet Int Med, 2001; 15:486-493. , open access article.


Three litters of Shetland Sheepdog pups born to the same bitch and 2 different sires were studied because of uncontrollable seizures or progressive neurologic dysfunction. Four pups from the 1st litter, 1 from the 2nd litter, and 4 from the 3rd litter had severe diffuse spongy degeneration of the white matter of the brain and spinal cord. An inherited basis for this syndrome was suspected. The purpose of this study was to evaluate the pups with currently available screening tests for the metabolic, biochemical, infectious, and toxicologic causes of leukodystrophy seen in humans and animals. Computed tomography scans revealed diffuse hypomyelination in the affected pup. Complete postmortem examination, including histopathology and electron microscopy, delineated a leukodystrophy resembling human Canavan's disease, but amino acid and organic acid metabolism abnormalities were not detected. No etiology for Shetland Sheepdog leukodystrophy has been found, but this condition represents another familial disease in the purebred dog population.
Departments of Small Animal Clinical Sciences & Veterinary Pathology, Michigan State University Veterinary Teaching Hospital, East Lansing, MI.

Nakahata, K, Uzauka Y, Matsumoto H, et. al: Hyperkinetic Involuntary Movements in a Young Shetland Sheepdog, J Am Anim Hosp Assoc, vol 28, 347-348, 1992



• Collie eye anomaly
Fredholm M, Larsen RC, Jönsson M, et al. Discrepancy in compliance between the clinical and genetic diagnosis of choroidal hypoplasia in Danish Rough Collies and Shetland Sheepdogs. Animal Genetics, 2016; 47:250-252. doi: 10.1111/age.12405
Collie eye anomaly (CEA) is a congenital, inherited ocular disorder which is widespread in herding breeds. Clinically, the two major lesions associated with CEA are choroidal hypoplasia (CH) and coloboma, and both lesions are diagnosed based on ophthalmological examination. A 7.8-kb intronic deletion in the gene encoding non-homologous end-joining factor 1 (NHEJ1) has been reported to be the causative mutation underlying CH when present in the homozygous state. In this study, we have investigated the compliance between the clinical and genetic diagnosis of CH in the Danish Rough Collie and Shetland Sheepdog populations. Our results show that the deletion inNHEJ1 is not predictive for CH in the Danish Rough Collie population, whereas the clinical and genetic diagnosis is in accordance with each other in the Shetland Sheepdog population. Based on these results, it can be concluded that the intronic deletion in NHEJ1 is not the causative mutation but, rather, a marker linked to the locus underlying the trait in some populations but linked to both the wild-type and CH-causing locus in most dogs in the Danish Rough Collie population.

Parker HG, Kukekova AV, Akey DT, Breed relationships facilitate fine-mapping studies: a 7.8-kb deletion cosegregates with Collie eye anomaly across multiple dog breeds. Genome Res. 2007; 17: 1562-1571. . Full text available online for free.
…. This work both establishes that the primary cea mutation arose as a single disease allele in a common ancestor of herding breeds as well as highlights the value of comparative population analysis for refining regions of linkage.
From various institutions in the U.S.

Bedford PG. Collie eye anomaly in the United Kingdom. Veterinary Record, 1982; 111:263-270.
Approximately 2500 rough collies, smooth collies and Shetland sheepdogs were examined during a three year period in an attempt to establish the incidence of collie eye anomaly in the United Kingdom and to produce data on the hereditability of the disease. The overall incidence in the two collie breeds was approximately 64 per cent, but the disease was seen with slightly more frequency in the Shetland sheepdog, 72 per cent of the dogs examined being affected. Pedigree analysis and test mating has confirmed the opinion held in the USA that the disease is inherited as an autosomal recessive trait. In this report the pleomorphism of the disease in these three breeds is discussed together with the inherent problems in diagnosis.

Barnett KC, Stades FC. Collie eye anomaly in the Shetland Sheepdog in The Netherlands. J Small Anim Prac. 1979; 20: 321-329.
The eyes of a group of Shelties and Collies were examined for Collie Eye Anomaly and Progressive Retinal Atrophy, and any other eye abnormality noted. The incidence of CEA in 120 Shetland Sheepdogs was over 48%. There were no cases of PRA. Other abnormalities noted were distichiasis, hyaloid artery remnants, corneal lipidosis, persistent pupillary membranes, cataract and various retinopathies.
One group of an old type of Shetland Sheepdog, inbred for several generations, showed no signs of CEA. The significance of this finding is discussed.
Cataracts were present in nine dogs, all were partial and the majority only visible on slit lamp ...
Animal Health Trust Small Animals Centre, Lanwades Park, Kennett, Newmarket, Suffolk, England, and Faculteit der Diergeneeskunde van de Rijksuniversiteit te Utrecht, The Netherlands.

• Corneal dystrophy
Cooley PL, Dice PF. Corneal Dystrophy in the dog and cat. Vet Clin North Am Small Anim Pract. 1990; 20:681-92.
Two types of epithelial dystrophy have been described in dogs, one each in the Boxer and Shetland Sheepdog breeds, both of which can be associated with corneal erosions. Medical therapy is recommended when erosions or tear film abnormalities are present. Stromal dystrophies documented in dogs appear to be a primary lipid deposition in various layers of the stroma, depending on the breed. Stromal dystrophies seldom lead to loss of vision, but vision loss has been observed in middle aged Airedale Terriers and aged Siberian Huskies. Treatment is usually unnecessary. The dog demonstrates two types of endothelial dystrophy, one of which (posterior polymorphous dystrophy in the American Cocker Spaniel) does not lead to corneal edema. Endothelial dystrophy observed in the Boston Terrier, Chihuahua, and other breeds is associated with progressive corneal edema, which can lead to bullous keratopathy and corneal erosions. Stromal and endothelial dystrophies, both of which are associated with rapid progression of corneal edema, occur rarely in the cat. Treatment of dystrophies with progressive corneal edema is symptomatic and palliative.

Animal Eye Clinic, Seattle, Washington.

Dice PF: Corneal dystrophy in the Shetland Sheepdog. J Am Anim Hosp Assoc. 1986; 22: 655.

Dice PF. Corneal dystrophy in the Shetland sheepdog, in. Proceedings. Am Coll Vet Ophthalmol 1984; 15:241–242.

Crispin SM, Barnett KC. Dystrophy, degeneration and infiltration of the canine cornea. J Small Anim Prac, 1983; 24: 63-83.
Three conditions of the cornea in the dog are described; a form of corneal dystrophy (central/paracentral lipid dystrophy, lipidosis, lipoidosis, cholesterolosis), degeneration (fatty and calcareous degeneration) and infiltration (arcus lipoides corneae, anterior embryotoxon, pre-senile arcus). The clinical appearance, together with histopathological and ultrastructural details, are recorded. The age, sex, breed incidence and possible hereditary factors are also included. Reference is made to previous reports in the veterinary literature and the three conditions are compared with similar conditions in man.
Four breeds, namely the Rough Collie, Shetland Sheepdog, Cavalier King Charles Spaniel and Alsatian (German Shepherd Dog), account for over two thirds of the total cases seen.
Department of Anatomy, Royal (Dick) School of Veterinary Studies, Summerhall, Edinburgh

• Progressive retinal atrophy

Wiik AC, Ropstad EO, Ekesten B, et al. Progressive retinal atrophy in Shetland sheepdog is associated with a mutation in the CNGA1 gene. Animal Genetics, 2015; 46:515-521. doi: 10.1111/age.12323
Progressive retinal atrophy (PRA) is the collective name of a class of hereditary retinal dystrophies in the dog and is often described as the equivalent of retinitis pigmentosa in humans. PRA is characterized by visual impairment due to degeneration of the photoreceptors in the retina, usually leading to blindness. PRA has been reported in dogs from more than 100 breeds and can be genetically heterogeneous both between and within breeds. The disease can be subdivided by age at onset and rate of progression. Using genome-wide association with 15 Shetland Sheepdog (Sheltie) cases and 14 controls, we identified a novel PRA locus on CFA13 (Praw = 8.55 × 10−7,Pgenome = 1.7 × 10−4). CNGA1, which is known to be involved in human cases of retinitis pigmentosa, was located within the associated region and was considered a likely candidate gene. Sequencing of this gene identified a 4-bp deletion in exon 9 (c.1752_1755delAACT), leading to a frameshift and a premature stop codon. The study indicated genetic heterogeneity as the mutation was present in all PRA-affected individuals in one large family of Shelties, whereas some other cases in the studied Sheltie population were not associated with this CNGA1 mutation. To our knowledge, this is the first report of a mutation in CNGA1 causing PRA in dogs.
The above work was done in Norway and Sweden.

Karlstam L, Hertil E, Zeiss C, et al. A slowly progressive retinopathy in the Shetland Sheepdog. Veterinary Ophthalmology, 2011; 14:227–38. doi: 10.1111/j.1463-5224.2010.00866.x.

From Sweden.


To describe a slowly progressive retinopathy (SPR) in Shetland Sheepdogs. Animals  Forty adult Shetlands Sheepdogs with ophthalmoscopic signs of SPR and six normal Shetland Sheepdogs were included in the study.
Ophthalmic examination including slit-lamp biomicroscopy and ophthalmoscopy was performed in all dogs. Electroretinograms and obstacle course-test were performed in 13 affected and 6 normal dogs. The SPR dogs were subdivided into two groups according to their dark-adapted b-wave amplitudes. SPR1-dogs had ophthalmoscopic signs of SPR, but normal dark-adapted b-wave amplitudes. Dogs with both ophthalmoscopic signs and subnormal, dark-adapted b-wave amplitudes were assigned to group SPR2. Eyes from two SPR2 dogs were obtained for microscopic examination.
The ophthalmoscopic changes included bilateral, symmetrical, greyish discoloration in the peripheral tapetal fundus with normal or marginally attenuated vessels. Repeated examination showed that the ophthalmoscopic changes slowly spread across the central parts of the tapetal fundus, but did not progress to obvious neuroretinal thinning presenting as tapetal hyper-reflectivity. The dogs did not appear seriously visually impaired. SPR2 showed significantly reduced b-wave amplitudes throughout dark-adaptation. Microscopy showed thinning of the outer nuclear layer and abnormal appearance of rod and cone outer segments. Testing for the progressive rod-cone degeneration ( prcd )-mutation in three dogs with SPR was negative.
Slowly progressive retinopathy is a generalized rod-cone degeneration that on ophthalmoscopy looks similar to early stages of progressive retinal atrophy. The ophthalmoscopic findings are slowly progressive without tapetal hyper-reflectivity. Visual impairment is not obvious and the electroretinogram is more subtly altered than in progressive retinal atrophy. The etiology remains unclear. SPR is not caused by the prcd-mutation.

• Ocular - other
Hamor RE, Roberts SM, Severin GA, Evaluation of results for Schirmer tear tests conducted with and without application of a topical anesthetic in clinically normal dogs of 5 breeds. Am J Vet Res. 2000; 61: 1422-1425.

Objective—To evaluate, for clinically normal dogs, results of Schirmer tear tests in eyes without topical anesthetic (STT) and to detect differences associated with breed, sex, age, day, and time of day in eyes in which STT was performed after use of topical anesthetic (STTa).
Animals—41 Beagles, 43 Labrador Retrievers, 25 Golden Retrievers, 26 English Springer Spaniels, and 22 Shetland Sheepdogs.
Procedure—Beagles had STT and STTa values measured twice daily for 5 days. Client-owned dogs of 4 other breeds had STT and STTa values measured once.
Results—Mean ± SD values of Beagles for STT and STTa were 20.2 ± 2.5 and 3.8 ± 2.7 mm/min. Mean values for STT and STTa were as follows: Labrador Retriever, 22.9 ± 4.1 and 9.6 ± 3.8 mm/min; English Springer Spaniel; 20.7 ± 3.2 and 5.4 ± 3.4 mm/min; Golden Retriever, 21.8 ± 3.7 and 8.8 ± 3.1 mm/min; and Shetland Sheepdog, 15.8 ± 1.8 and 3.6 ± 2.8 mm/min. Overall mean values for STT and STTa were 20.2 ± 3.0 and 6.2 ± 3.1 mm/min. Differences for STT and STTa were detected among breeds, but significant differences were not associated with sex or age within each breed or in overall values for all dogs.
Conclusions and Clinical Relevance—Results for the STT reported here compare favorably with reported values, except for results of Shetland Sheepdogs; however, results for the STTa differ dramatically from reported values. Clinicians should consider effects attributable to breed when evaluating results of STT and STTa in dogs.
Department of Clinical Sciences, Colorado State University College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado CO 80523.

Orthopedic Disorders

• Superficial digital flexor tendon injury

Solanti SI, Laitinen O, Atroshi F. Hereditary and clinical characteristics of lateral luxation of the superficial digital flexor tendon in Shetland sheepdogs. Vet Ther, 2002; 3:97-103.
Department of Clinical Veterinary Sciences, Faculty of Veterinary Medicine, University of Helsinki, Finland
A study was conducted to define the mode of inheritance of lateral luxation of the superficial digital flexor (SDF) tendon in different lines of Shetland sheepdogs by examination of pedigree data. This pedigree analysis included affected and unaffected dams, sires, and offspring; common clinical signs; and age at onset. The clinical, histopathologic, and radiographic features of the disease were also studied. Of the 14 offspring from five matings of an affected sire to unrelated affected females, 100% were affected with lateral luxation of the SDF tendon. Of the 59 offspring from the same affected sire to unrelated, unaffected females, 44% were affected. The mating between normal parents produced 61% unaffected and 39% affected offspring. Application of the phenotypic findings in this study to a Mendelian genetic model of inheritance suggests that lateral luxation of the superficial digital tendon in Shetland sheepdogs is inherited as a simple autosomal recessive trait.

Hoscheit LP. Luxation of the tendon of the superficial digital flexor muscle in two dogs. Can Vet J, 1994; 35:120-1. No abstract available.
Dogs in the above article were a Collie and Collie cross.

Mauterer JV Jr, Prata RG, Carberry CA, et al. Displacement of the tendon of the superficial digital flexor muscle in dogs: 10 cases (1983-1991). J Am Vet Med Assoc., 1993; 203:1162-1165.
Displacement of the tendon of the superficial digital flexor muscle was diagnosed in 9 dogs (10 tarsi). Four of 10 displacements occurred in Shetland Sheepdogs. All dogs had an acute onset of lameness with swelling over the proximal end of the tuber calcanei. Lateral displacement occurred in 8 tarsi and medial displacement in 2 tarsi. Nonsurgical treatment (exercise restriction, bandaging, and administration of anti-inflammatory medication) was ineffective in the 5 dogs in which it was attempted. Surgical reconstruction of the supporting soft tissues resulted in return to normal function in 9 cases available for follow-up evaluation.
PMID: 8244865 [PubMed - indexed for MEDLINE]

Bernard MA. Superficial digital flexor tendon injury in the dog. Can Vet J, 1977; 18:105–107.
PMCID: PMC1697523,

Three of the 5 dogs affected were Shelties.

• Other

Jaeger GH, Marcellin-Little DJ, Ferretti A. Morphology and correction of distal tibial valgus deformities. J Small Anim Pract, 2007; 48:678-682. Retrospective Study.

OBJECTIVES: To characterise distal tibial valgus deformities in dogs through physical examination and radiographic evaluation. Methods: In a clinical study of 16 client-owned dogs, twelve unilateral and four bilateral distal tibial valgus deformities were evaluated using palpation and radiographs. The origin and amplitude of angulation, rotation and length deficits if present were measured. Radiographically, fibular length and position in relation to the tibia was compared in affected and clinically normal limbs. The dimensions of the fibular physes were also compared between clinically normal and affected limbs.

RESULTS: Rottweilers and Shetland sheepdogs were overrepresented. Valgus deformities ranged from 16 degrees to 48 degrees (median, 32 degrees ) in affected and from 0 degrees to 13 degrees (median, 6 degrees ) in contralateral, clinically normal limbs. Fibular length, fibular position relative to the tibia or physeal dimensions were not statistically different between affected and clinically normal limbs.

CONCLUSION AND CLINICAL RELEVANCE: Many distal tibial valgus deformities in dogs are a uniplanar deformity without concurrent craniocaudal or rotational changes or length deficits. A growth cessation in the fibula does not appear to be responsible for the development of the deformity.

Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USA.

Dupuis J, Breton L, Drolet R. Bilateral epiphysiolysis of the femoral heads in two dogs. J Am Vet Med Assoc, 1997;210:1162-1165.
Department of Clinical Sciences, Facultè de Medecine Vètèrinaire, Universite de Montrèal, St. Hyacinthe, PQ, Canada.
Two Shetland Sheepdogs that did not have a history of trauma were referred because of a gradual onset of lameness in the hind limbs. Bilateral slipped capital femoral epiphysis was diagnosed. Separation of the proximal femoral epiphysis that is not associated with trauma is recognized as a distinct clinical syndrome in adolescent human beings and swine, causing a condition called epiphysiolysis. The precise cause of this type of injury is unknown. Histologic lesions observed in the growth plates could have been the result of an abnormally high mechanical load imposed by obesity. It is not known whether cartilaginous lesions observed in the physis of 1 dog represented a preexisting cartilaginous defect (dyschondroplasia) or a late stage of repair after separation of the capital femoral epiphysis.

Taylor SM, Remedios A, Myers S. Craniomandibular osteopathy in a Shetland sheepdog. Can Vet J, 1995; 36: 437–439.

Owen LN, Bostock DE. Multiple cartilaginous exostoses with development of a metastasizing osteosarcoma in a Shetland Sheepdog. J Sm Anim Prac, 1971;12:507-512.
A case of multiple cartilaginous exostoses in an 8-year-old Shetland Sheepdog is described. One of the exostoses on the left scapula transformed into an osteosarcoma which metastasized to the lungs. This finding is unusual as in many cases described in man and in one case in a dog chondrosarcomas developed from the exostoses.
Department of Animal Pathology, School of Veterinary Medicine, Cambridge

Reproductive Disorders

Klaas P, Barth AD, Kiefer UT, et al. Retrograde ejaculation in a Shetland sheepdog. Can Vet J, 1992; 33:53-55.

Pendergrass TW, Hayes Jr HM. Cryptorchism and related defects in dogs: Epidemiologic comparisons with man. Teratology, 1975;12: 51–55. doi: 10.1002/tera.1420120107
In a study of 1266 dogs with cryptorchism from a large clinic/ hospital series 8 breeds were found to be at excess risk of the defect and 3 breeds at significantly low risk. Review of the medical histories revealed that hip dysplasia, patellar dislocation, defects of the penis and prepuce, and umbilical hernia were excessively associated with cryptorchism. Testicular tumors were diagnosed 10.9 times more commonly among cryptorchid dogs. The epidemiologic features of canine cryptorchism were compared with those in man. Cryptorchid dogs could be used as models for etiologic research. (... Eight breeds were at significantly high risk: Chi- huahua, Miniature Schnauzer, Pomeran- ian,
Poodle (both the miniature and toy breeds and the standard breed), Shetland Sheepdog, Siberian Husky, and Yorkshire Terrier.)

Skin Disorders

• Dermatomyositis

Wahl JM, Clark LA, Skalli O, et al. Analysis of gene transcript profiling and immunobiology in Shetland sheepdogs with dermatomyositis. Vet Dermatol, 2008; 19:52-58.

Dermatomyositis (DM) is a canine and human inflammatory disease of the skin and muscle that is thought to be autoimmune in nature. In dogs, DM occurs most often in the rough collie and Shetland sheepdog. Characteristic skin lesions typically develop on the face, ears, tail, and distal extremities. The severity of lesions varies and is thought to increase with stressful stimuli. Previous studies in the collie suggest that DM is inherited in an autosomal dominant fashion with incomplete penetrance. The work presented here concerns gene transcripts profiling and immunobiology of DM in the Shetland sheepdog. Gene transcript profiles were generated for affected and normal skin using a canine-specific oligonucleotide array having 49,929 probe sets. Two-hundred and eight-five gene transcripts, many of which are involved in immune function, were found to be differentially regulated in these tissues. Also reported are Western blot, immunohistochemistry, and immunofluorescence analyses which showed that staining patterns with sera from normal and affected dogs are quite similar. While our work suggests that canine DM is a disease that may be immune mediated, it did not detect the production of specific disease-associated autoantibodies.

Department of Pathobiology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA.

Clark LA. Credille KM. Murphy al. Linkage of dermatomyositis in the Shetland Sheepdog to chromosome 35. Vet Dermatol, 2005; 16:392-394.

Dermatomyositis is an inflammatory disease of the skin and muscle and is most commonly found in the Shetland sheepdog. Both the clinical presentation and the age of onset of dermatomyositis vary widely, and the inability to diagnose dermatomyositis before clinical symptoms ensue has made control of the disease difficult. Identification of a genetic marker that cosegregates with dermatomyositis would facilitate the development of a DNA-based test for the early detection of affected dogs. We report the use of linkage disequilibrium (LD) mapping to identify linkage to phenotypic dermatomyositis in the Shetland sheepdog. One marker, microsatellite marker FH3570 on canine chromosome 35, had evidence of LD (P=0.00002). Further studies are necessary to narrow the region harbouring the dermatomyositis locus, identify candidate genes and determine mode of inheritance.

Department of Pathobiology, College of Veterinary Medicine and Biomedical Sciences, Texas A+M University, College Station, TX 77843, USA.

Ferguson EA, Cerundolo R, Lloyd DH,et al. Dermatomyositis in five Shetland sheepdogs in the United Kingdom. Vet Rec, 2000; 146:214-217.

Five cases of dermatomyositis in four Shetland sheepdog puppies and one adult bitch are described. The dogs all had well-defined patches of scaling, crusting and alopecia over the muzzle, periorbital skin and distal limbs, and the tail, perineum and pinnae were affected in some of them. The affected puppies were all sired by the same stud dog. The affected adult bitch was unrelated to the puppies. Three of the four dogs tested had high serum creatine kinase concentrations and electromyographic abnormalities were detected in three of the four dogs tested. The histological changes observed in the skin of four of the dogs strongly supported the diagnosis of dermatomyositis, and in the fifth dog they were compatible with this diagnosis. Two of the puppies were euthanised shortly after being diagnosed. In the other two puppies and the adult the disease remains stable and non-progressive 15 to 18 months after diagnosis. The sire of the four affected puppies has been used extensively because it was considered to be genetically clear of collie eye anomaly.

Department of Small Animal Medicine and Surgery, The Royal Veterinary College, North Mymms, Hatfield.

Hargis AM, Mundell AC: Familial canine dermatomysositis. Comp Cont Educ, 1992;14:855.

Hargis AM, Prieur DJ, Haupt KH. Post-mortem findings in a Shetland sheepdog with dermatomyositis. Vet Path, 1986; 23: 509-511.

Haupt KH, Prieur DJ, Moore MP, et al: Familial canine dermatomyositis: Clinical, electrodiagnostic, and genetic studies. Am J Vet Res, 1985; 46:1870.

Hargis AM, Haupt KH, Hegreberg GA, et al: Familial canine dermatomyositis: Initial charaterization of cutaneous and muscular lesions. Am J Pathol, 1984; 116: 234.

• Lupus

Jackson HA. Eleven cases of vesicular cutaneous lupus erythematosus in Shetland sheepdogs and rough collies: clinical management and prognosis. Vet Dermatol, 2004; 15:37-41.

A cutaneous ulcerative disease is recognized to affect the adult Shetland sheepdog and rough collie. This has a distinct clinical and histological appearance consistent with a vesicular variant of cutaneous lupus erythematosus (VCLE). Retrospective information on the clinical outcome and response to therapy was collected from 11 cases of histologically confirmed VCLE. In 8/11 dogs the onset of disease was in the summer; in three dogs recrudescence occurred in subsequent summers. In eight dogs the skin disease was judged to be 75-100% controlled with therapy after a minimum follow-up of 9 months. Successful treatment in seven of these cases comprised immunosuppressive doses of oral glucocorticoids, alone (one dog), in combination with azathioprine (five dogs) and doxycycline (one dog). One case responded to topical fluocinolone. Three dogs were euthanised for reasons directly related to the disease, one prior to initiating any therapy. Vesicular cutaneous lupus erythematosus in the rough collie and Shetland sheepdog can be a debilitating skin disease which is best managed with aggressive immunosuppressive therapy. Sun avoidance or the use of sunscreens is an important additional management recommendation.

Department of Clinical Sciences, North Carolina State University, College of Veterinary Medicine, 4700 Hillsborough Street, Raleigh, NC 27606, USA.

Comment: The disease above may have been dermatomyositis.

Jackson HA, Olivry T, Berget F, et al. Immunopathology of vesicular cutaneous lupus erythematosus in the rough collie and Shetland sheepdog: a canine homologue of subacute cutaneous lupus erythematosus in humans. Vet Dermatol, 2004; 15:230-239.

Clinical and histological features of an erosive disease in the rough collie and Shetland sheepdog are most consistent with a vesicular variant of cutaneous lupus erythematosus (VCLE). This paper reports the immunopathological findings of canine VCLE using samples from 17 affected dogs. Lesional skin sections were stained with monoclonal antibodies specific for CD3 (11 dogs) or a panel of monoclonal antibodies specific for leukocyte antigens (two dogs). Apoptotic cells were detected using the TUNEL method in 12 cases. Direct (14 dogs) and indirect immunofluorescence tests (five dogs) were also performed. Circulating antibodies to extractable nuclear antigens (ENA) were surveyed in 11 dogs by immunoblotting and ELISA. The predominant cells at the dermal-epidermal interface were identified as CD3(+) T lymphocytes expressing CD4 or CD8 and CD1(+) dendritic antigen presenting cells. In 7/12 dogs (58%), apoptosis of basal keratinocyte nuclei was present. Up-regulation of MHCII and ICAM-1 was observed on basal keratinocytes from the two dogs examined. Direct immunofluorescence revealed deposition of immunoglobulins bound to the cytoplasm of keratinocytes (6/14 dogs; 43%), to the dermal-epidermal junction (7/14 dogs; 50%), or to superficial dermal venules (13/14 dogs; 93%). Circulating IgG auto-antibodies targeting one or more ENA were detected in nine (82%) and eight (73%) of 11 dogs by immunoblotting and ELISA, respectively. These auto-antibodies recognized Ro/SSA and/or La/SSB in four (36%) and six (55%) of 11 dogs respectively by these two methods. Altogether, results of these studies provide evidence supporting the hypothesis that canine VCLE is an immunological homologue of subacute cutaneous lupus erythematosus in humans.

Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, NC 27606, USA.

Jackson HA, Olivry T. Ulcerative dermatosis of the Shetland sheepdog and rough collie dog may represent a novel vesicular variant of cutaneous lupus erythematosus. Vet Dermatol, 2001; 12:19-27. Case Reports.*

A syndrome of ulcerative dermatitis (UDSSC) previously has been described as unique to the Shetland sheepdog and rough collie dog. The pathogenesis of this disease is poorly understood and it has been suggested that it may be a variant of canine dermatomyositis (DM) which is also seen in these breeds. Information on the clinical presentation and previous medical history was collected from five Shetland sheepdogs and three rough collie dogs previously diagnosed with UDSSC. Characteristic features of the disease were adult onset in the summer months with annular, polycyclic and serpiginous ulcerations distributed over sparsely haired areas of the body. Skin biopsies taken from active lesions were compared in a blinded fashion with histological sections from seven Shetland sheepdogs and one rough collie with DM. Dermatomyositis was characterized histologically as a cell poor interface dermatitis associated with follicular atrophy. In contrast, the lesional pattern of UDSSC is that of a lymphocyte-rich interface dermatitis and folliculitis with vesiculation at the dermal-epidermal junction. The authors conclude that these represent two distinct diseases and that UDSSC may be a vesicular form of cutaneous lupus erythematosus seen in the adult rough collie dog and Shetland sheepdog.

North Carolina State University, College of Veterinary Medicine, 4700 Hillsborough Street, Raleigh, NC 27606, USA.

*This may have been dermatomyositis.

Urinary Tract Disorders

Bladder Cancer:

Decker B, Parker HG, Dhawan D, et al. Homologous Mutation to Human BRAF V600E Is Common in Naturally Occurring Canine Bladder Cancer—Evidence for a Relevant Model System and Urine-Based Diagnostic Test. Mol Cancer Res; 6:993-1002, 2015.

Conclusions: This study demonstrates the activating BRAF mutation (V600E), which is found in multiple human cancers, is a driver of canine InvTCC, and highlights a urine-based test for quick diagnosis.

The above study was supported by the ASSA and Sheltie owners participated in the research.

Renal Disease:

Dr. Whiteley published a rebuttal to the expression of concern in 2015.

Whiteley MH. Allelic variation in the canine Cox-2 promoter causes hypermethylation of the canine Cox-2 promoter in clinical cases of renal dysplasia: Clin Epigenetics. 2014; 6: 7.

Guimarães LL, Reis MO, Hesse KL, et al: Pathological findings in dogs with renal dysplasia in Southern Brazil. Pesq. Vet. Bras, 2014; 34:


Renal dysplasia results from a disturbance which occurs during nephrogenesis. The disease may be unilateral or bilateral, and leads to abnormal kidney differentiation leading to renal failure in young dogs. Several agents, including viruses, can cause the dysplasia till three months after birth, when the early nephron formation of the developing kidney is completed. Eleven renal dysplasia cases were diagnosed in 186 dogs with renal failure of 5,846 dogs necropsied in the Veterinary Pathology Sector, Federal University of Rio Grande do Sul, in the period 2002-2013. Tissue samples collected during necropsy were fixed in 10% formaldehyde and stained with hematoxylin-eosin (HE) and Masson’s trichrome protocol. Upon necropsy, kidneys were pale, smaller than normal, irregular and firm, and presented lower cortex diameter. Some exhibited cysts and whitish, parallel radially arranged striae in the medulla. Primary and secondary renal lesions were observed during histological examination. Primary lesions included fetal glomeruli and tubules, quantitative reduction in glomeruli, adenomatous tubules, and persistence of metanephric ducts. As for secondary lesions, Masson trichrome staining revealed intense interstitial fibrosis in all cases; furthermore, dilation of tubules and of Bowman’s capsules, glomerular atrophy, and glomerulosclerosis were observed. Even though most cases were associated with breed, the results obtained indicate high prevalence of renal dysplasia in mixed-breed dogs, possibly because they were the majority of animals referred for necropsy. Although primary lesions were easily identified using HE, Masson’s trichrome protocol is useful to characterize the extent of fibrosis.

Index terms: Dysplasia, kidney, dogs.

No Shelties were in this study.

The PLOS ONE Editors (2012) Expression of Concern: Novel Allelic Variants in the Canine Cyclooxgenase-2 (Cox-2) Promoter Are Associated with Renal Dysplasia in Dogs. 2012 doi: info:doi/10.1371/journal.pone.0049703 View expression of concern

Whiteley MH, Bell JS, Rothman DA.. Novel allelic variants in the canine cyclooxygenase-2 (Cox-2) promoter are associated with renal dysplasia in dogs. PlosOne 7:e16684. 2011

Only one Shetland Sheepdog was included in the above study and the “diagnosis” was made using ultrasound and bloodwork findings, no biopsy.

Nash AS. Familial renal disease in dogs. Journal of Small Animal Practice, 1989; 30: 178-183.

Juvenile renal disease in dogs has been encountered in over 20 breeds but in only nine of these (cocker spaniel, Norwegian elkhound, lhasa apso, shih tzu, samoyed, dobermann, standard poodle, soft-coated wheaten terrier and bull terrier) have familial nephropathies been reported, and in only two (samoyed and cocker spaniel) has the exact mode of inheritance been elucidated. Reasons for this unsatisfactory state of affairs are: 1 Renal failure in young dogs may not be due to a familial nephropathy, and while helpful diagnostic information may be gained from blood and urine analysis, accurate diagnosis of the specific type of renal disease requires examination of renal biopsy or post mortem material by an experienced pathologist. 2 Not all affected animals show clinical signs at the same age, making collection of data, often from widely dispersed animals, both difficult and slow. 3 The disease process in one breed may be very different from that in another, so that each breed has to be investigated separately. 4 There has to be a willing determination to face the problem by individual breed clubs, with the commitment of a large number of breeders, owners and veterinary surgeons.
Shetland Sheepdogs were one of many in a list of breeds with dogs having been diagnosed as having juvenile renal disease, but in which “familial basis has not been proved.”