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
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