Genetic basis - Gall bladder mucocele (GBM) formation in Shetland Sheepdogs is linked to a genetic mutation in the ABCB4 gene. Specifically, the insertion of a single guanine base (G) in exon 12 (c.1583_1584insG or c.1660_1661insG, depending on reporting) results in a frameshift and four premature stop codons, leading to a severely truncated and dysfunctional ABCB4 protein. This protein normally acts as a phosphatidylcholine transporter in hepatocytes. Early reports proposed a dominant mode of inheritance with incomplete penetrance; however, subsequent research suggests that the inheritance is more complex, likely multifactorial, and the mutation alone is not always sufficient to cause disease
Pathophysiology - The ABCB4 protein helps maintain the integrity of biliary tract epithelia by secreting phospholipids into bile. Without functional ABCB4, there is less protection for the gallbladder lining from bile salts, leading to chronic epithelial injury, mucin overproduction, hyperplasia of gallbladder epithelium, and eventually mucocele formation. This results in a build-up of excessive, abnormal mucus in the gallbladder, which can obstruct bile flow and cause severe hepatobiliary disease
Complications - Biliary obstruction and possible rupture. Peritonitis (if rupture occurs). Jaundice and liver dysfunction. Severe, potentially fatal abdominal pain and systemic illness. Surgical removal of the gallbladder (cholecystectomy) is a common and sometimes urgent intervention.
Why This Matters to Breeders and Vets - Gall bladder mucocele is a significant health concern for Shetland Sheepdogs, leading to pain, surgery, or death. For breeders, understanding the uncertain genetic mechanism helps guide more informed, cautious breeding. For veterinarians, awareness of the breed predilection and genetic factors supports early diagnosis and treatment, improves outcomes, and empowers client education about preventative care, risk assessment, and the limitations of current genetic tests.