COMPOSITIONS AND METHODS FOR DIAGNOSIS AND TREATMENT OF HEPATOBILIARY DISEASE AND ASSOCIATED DISORDERS

摘要

Provided are nucleic acids comprising ABCB4 gene mutations (e.g., insertions, deletions, frame shift, missense) (e.g., canine ABCB4 1583_1584G) that result in prematurely terminated and/or inactive ABCB4 proteins. A significant association (P=1.54E-7) of the mutations was detected between gallbladder mucoceles-affected dogs, providing methods for detection or diagnosis of a hepatobiliary disease and/or related conditions (e.g., increased mucin secretion, mucinous hyperplasia, gallbladder mucocele, progressive familial intrahepatic cholestasis (type 3), cholelithiasis, primary biliary cirrhosis, and intrahepatic cholestasis of pregnancy). Compositions and methods for genotyping or screening of test subjects are provided, and have added utility in combination with surgical intervention, selective breeding, and medical or dietary management. Also provided are methods of treatment of dogs with hepatobiliary disease, comprising administration of hydrophilic, less cytotoxic bile acids (e.g., ursodeoxycholate). Methods for screening or testing for therapeutic agents for treatment of human hepatobiliary disease, comprising use of canine test subjects harboring ABCB4 gene mutations are provided.