ASSA Previous Studies

Investigation of Gallbladder Disease and Hypercholesterolemia in Shetland Sheepdogs – update

Dr. Katrina Mealey and others expanded the original research (below) to include a much larger population of dogs. DNA samples from multiple dog breeds were evaluated for the presence or absence of the genetic mutation that has been associated with the formation of gallbladder mucoceles in Shelties. The number of samples studied was much larger than those used in the original work on Shelties. As in the earlier study, samples from dogs with and without (control dogs) gallbladder mucoceles were evaluated; however, the “control” dogs in the more recent study were age-matched, but not exclusively older, normal dogs as were used in the Sheltie only study.

The results of the more recent work were less definitive than the 1st study, as there were some false positives and false negatives: some dogs had the diagnosis of gallbladder mucoceles that did not have the genetic mutation (false negative) and others had the mutation without the diagnosis of gallbladder mucoceles (false positive). The investigators concluded that there was no statistically significant correlation between the genetic mutation and the formation of gallbladder mucoceles in Shelties or other breeds. This study resulted in the following publication:

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 May 2014 vol. 26 no. 3 434-436. http://vdi.sagepub.com/content/26/3/434.full

Summary:
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.

Investigation of Gallbladder Disease and Hypercholesterolemia in Shetland Sheepdogs. Primary investigator: Katrina Mealey DVM PhD, College of Veterinary Medicine, Washington State University.

This study began in 2008. The ASSA assisted Dr. Mealey in collection of DNA samples from Shelties with and without hyperlipidemia and gallbladder disease by sending notice of the study through Sheltie related internet message groups and posting the information on the ASSA web page. Nine months after the study began, enough material was obtained, through the generous participation of Sheltie owners, to limit sample collection to dogs with surgically confirmed gallbladder mucoceles and older normal Shelties. It was a mere 18 months from the beginning of ASSA participation until a genetic mutation was found. This study resulted in the following publication:

Mealey KL, Minch JD, White SN, Snekvik KR, Mattoon JS: An insertion mutation in ABCB4 is associated with gallbladder mucocele formation in dogs. Comp Hepatol. 2010 Jul 3;9:6. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2904718/?tool=pubmed

2000 – 2016:
Collie Health Foundation and the ASSA Foundation have supported research on DMS since the early 2000’s through monetary grants and encouraging participation by Collie and Sheltie owners. Much of the research was done at Texas A&M University by Drs. Christine Rees, Leigh Anne Clark, and Keith Murphy. Dr. Rees is now in private practice in Texas. Drs. Clark and Murphy are now working at Clemson University, Clemson, SC. The research has resulted in at least 2 scientific publications (1, 2).
Current research on DMS is now being done in Dr. Clark’s laboratory and has resulted in finding causative genetic mutations. A manuscript on the findings is in progress. In 2013, Dr. Clark received funding from the National Institutes of Health (NIH) for over $200,000 to search for research on DMS: Naturally Occurring Dog Model For Juvenile Dermatomyositis. Project #: 1R15AR062868-01A1. Link to the NIH site with the project details.

(1) Wahl JM, Clark LA, Skalli O, Ambrus A, Rees CA, Mansell JL, Murphy KE: Analysis of gene transcript profiling and immunobiology in Shetland sheepdogs with dermatomyositis. Vet Dermatol. 2008, 19(2):52-8. www.ncbi.nlm.nih.gov/pubmed/18336421

(2) Clark LA, Credille KM, Murphy KE, Rees CA: Brief communication, Linkage of dermatomyositis in the Shetland Sheepdog to chromosome 35. Vet Dermatol. 2005, 16:392-394. http://www3.interscience.wiley.com/journal/118705211/abstract

2010:
Dermatomyositis Research - Treatment Study, February, 2010

While at Texas A & M University, Dr. Christine Rees investigated the use of Dapsone as an alternative treatment to Trental (pentoxifylline) for dogs with DM*. Dapsone is an oral medication found to be effective in the treatment of DM in humans. The following is a report from Sherry Lindsey RN BSN on the results of the study. Sherry has worked closely with the researchers at Texas A & M and has maintained an extensive website on DM in Shelties.

“The best treatment option for DM symptoms continues to be Trental or pentoxifylline. It is recommended that brand name be used rather than generic. The dose used in the study is 25 to 30 milligrams per kilogram of body weight every 12 hours given by mouth and always with food. These tablets have been successfully split when used in treating the DM study dogs. Dapsone was also studied and could be used as an alternative in those rare dogs who do not tolerate Trental. The Dapsone dose in the study was 1 milligram per kilogram of body weight every eight hours, given by mouth. However, several dogs did well after being on the Dapsone for a month or two at 1 milligram per kilogram of body weight every 12 hours, by mouth.”

Contacts for DM information/questions:
Sherry Lindsey RN BSN is a longtime Sheltie breeder who assisted Dr. Rees in all of the DM studies and housed and cared for the DM study dogs. She is happy to answer any questions concerning DM and may be reached at shalainetx@aol.com. A website with DM information, including photos of DM affected dogs, may be found at www.shalaine.com/DM/DM.html

*The current abbreviation for dermatomyositis is DMS.

In 2013, the Research Advisory Committee received communication from Andrew Lundquist, MD, PhD of the Broad Institute, Cambridge, MA announcing a call for blood samples from Shelties with renal dysplasia or any form of kidney disease. He and others at the Broad Institute had been working on the genetics of renal dysplasia in Boxers. They had identified a region of interest that contained a gene that is commonly affected in human cases of renal dysplasia and wanted to obtain blood samples from other breeds of dogs to advance their research. Information about this study was posted on the ASSA website. Unfortunately, Dr. Lundquist has left the Broad Institute and the ASSA has not received further contact from researchers at the Institute.