All Phenotypes Hnf1b<tm1Mya> MGI Mouse

premature death ( J:75935 )

• despite the severity of their phenotype, most mutant mice survive for several months

abnormal hepatobiliary system morphology ( J:75935 )

• mutants exhibit abnormal intrahepatic bile duct (IHBD) differentiation and morphogenesis, resulting in persistence of the ductal plate and a highly disorganized biliary system

• in addition, mutant livers show absence of interlobular arteries in portal tracts, suggesting a link between arterial and biliary development within the liver

abnormal extrahepatic bile duct morphology ( J:75935 )

• at 2 months, mutant extrahepatic biliary tracts display epithelial abnormalities

abnormal cystic duct morphology ( J:75935 )

• in extreme cases, the cystic duct is completely dilated and no duct is clearly identifiable

abnormal intrahepatic bile duct morphology ( J:75935 )

• at 2 months, mutants exhibit dysplasia of the larger intrahepatic bile ducts (IHBDs) and a reduction, or paucity, of small IHBDs

abnormal interlobular bile duct morphology ( J:75935 )

• absence of identifiable IHBDs is already evident at P7, indicating lack of formation of interlobular bile ducts

abnormal gallbladder epithelium morphology ( J:75935 )

• at 2 months, mutant gallbladders exhibit epithelial dysplasia

• in the mutant gallbladder, the normal cuboidal epithelium is replaced in some areas by a stratified squamous epithelium or mucus-secreting cells

• nonetheless, mutant gallbladders are filled with bile and communicate with the liver and the duodenum

enlarged liver ( J:75935 )

• mutant mice exhibit fully penetrant liver hypertrophy

hepatic necrosis ( J:75935 )

• at 2 months, mutant livers display hepatocyte necrosis and oval cell proliferation

abnormal hepatobiliary system physiology ( J:75935 )

liver inflammation ( J:75935 )

• at 2 months, mutant mice exhibit liver inflammation

abnormal bile duct physiology ( J:75935 )

intrahepatic cholestasis ( J:75935 )

decreased liver function ( J:75935 )

jaundice ( J:75935 )

• mutant mice exhibit fully penetrant chronic jaundice

increased circulating bilirubin level ( J:75935 )

• as early as P7, mutant mice show increased plasma levels of bilirubin

• by 2 months, mutant bilirubin and bile acid levels are dramatically increased

abnormal lipid homeostasis ( J:75935 )

increased circulating cholesterol level ( J:75935 )

• as early as P7, mutants exhibit significantly increased levels of serum cholesterol; levels become stabilized after P14

increased circulating triglyceride level ( J:75935 )

• as early as P7, mutants exhibit significantly increased levels of serum triglycerides, suggesting altered hepatocyte metabolism; levels become stabilized after P14

decreased body size ( J:75935 )

decreased body weight ( J:75935 )

• body weight differences are detected as early as P2 and increase with time, reaching a growth plateau at weaning

cachexia ( J:75935 )

postnatal growth retardation ( J:75935 )

• mutant mice display severe postnatal growth retardation