Phenotypes Associated with This Genotype

Genotype
MGI:5437134

• Allelic Composition: Nr1h4^tm1Gonz/Nr1h4^tm1Gonz
• Genetic Background: involves: 129X1/SvJ * C57BL/6

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

liver/biliary system

increased hepatocyte apoptosis ( J:118204 )

• TUNEL staining indicates increased hepatocyte apoptosis as mutants age

liver inflammation ( J:118204 )

abnormal liver morphology ( J:118204 )

• starting at 9 months of age, some mutants display preneoplasms in the liver, with small foci becoming obvious at 12 months of age

• liver damage includes many vaculoles due to lipid deposits, vaculation due to cell damage, inflammation, and focal necrosis

• significant amounts of BrdU+ cells are detected around the damaged regions of the liver suggesting initiation of a compensatory regenerative proliferation

focal hepatic necrosis ( J:118204 )

enlarged liver ( J:118204 )

• enlarged liver is not completely due to tumor formation because hepatomegaly is seen before tumors are observed

increased liver tumor incidence ( J:118204 )

• both males and females develop liver tumors at 15 months of age of varying severity

• mutants fed a diet containing 2% cholestyramine, a bile acid-sequestering resin, for 3 months starting at 11 months of age when they do not have tumors, have a significantly reduced number and size of liver malignant lesions when they are older

increased hepatocellular carcinoma incidence ( J:118204 )

• tumors are typical hepatocellular adenoma and carcinoma

increased liver adenoma incidence ( J:118204 )

• tumors are typical hepatocellular adenoma and carcinoma

neoplasm

increased liver tumor incidence ( J:118204 )

• both males and females develop liver tumors at 15 months of age of varying severity

• mutants fed a diet containing 2% cholestyramine, a bile acid-sequestering resin, for 3 months starting at 11 months of age when they do not have tumors, have a significantly reduced number and size of liver malignant lesions when they are older

increased hepatocellular carcinoma incidence ( J:118204 )

• tumors are typical hepatocellular adenoma and carcinoma

increased liver adenoma incidence ( J:118204 )

• tumors are typical hepatocellular adenoma and carcinoma

cellular

increased hepatocyte apoptosis ( J:118204 )

• TUNEL staining indicates increased hepatocyte apoptosis as mutants age

focal hepatic necrosis ( J:118204 )

homeostasis/metabolism

increased circulating aspartate transaminase level ( J:118204 )

• levels of alanine aminotransferase (ALT) are much higher in aging mutants than in controls, indicating increased liver damage

increased bile salt level ( J:118204 )

• serum and liver bile acid levels are higher in aging mutants than in wild-type controls

immune system

liver inflammation ( J:118204 )

growth/size/body

enlarged liver ( J:118204 )

• enlarged liver is not completely due to tumor formation because hepatomegaly is seen before tumors are observed

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
hepatocellular carcinoma		DOID:684	OMIM:114550	J:118204 , J:170790