Phenotypes for Nr1h4 MGI:2175162 MGI Mouse

increased susceptibility to induced morbidity/mortality ( J:64792 )

• about 30% of mutants die by day 7 when placed on a 1% cholic acid diet

• body weight is about 20% less than in wild-type mice, regardless of age

cachexia ( J:64792 )

• mutants on a 1% cholic acid diet exhibit severe wasting

decreased susceptibility to weight gain ( J:64792 )

• mutants on a 1% cholic acid diet exhibit a progressive decrease in body weight that results in about 1/3 of the initial body weight by day 5 of the diet

enlarged liver ( J:121075 )

• liver size, as a percentage of body weight, is higher than in wild-type mice at 12 months of age

increased circulating cholesterol level ( J:64792 )

• mutants on a regular diet or on a 1% cholesterol diet exhibit increased serum total cholesterol levels

increased circulating phospholipid level ( J:64792 )

• mutants on a regular diet or on a 1% cholesterol diet exhibit increased phospholipid levels

increased circulating triglyceride level ( J:64792 )

• mutants on a regular or a 1% cholesterol diet exhibit increased triglyceride levels

decreased body temperature ( J:64792 )

• mutants on a 1% cholic acid diet exhibit hypothermia

abnormal bile salt homeostasis ( J:64792 )

• mutants on a regular diet and 1% cholic acid diet have fecal bile acid excretion about 2-fold and 4-fold, respectively, lower than in wild-type

• mutants on a 1% cholic acid diet exhibit higher (7-fold) urinary bile acid excretion rates than wild-type on the same diet

abnormal bile salt level ( J:64792 )

• mutants on a regular diet exhibit an 8-fold increase in total serum bile acid concentration

• mutants on a 1% cholic acid diet exhibit an 23-fold increase in total serum bile acid concentration

• mutants on a regular or 1% cholic acid diet have lower bile acid pool (about by 2 fold) than wild-type

increased bile salt level ( J:121075 )

• 3-fold and 5.6-fold increase in serum bile acid levels in young and older mutants, respectively, compared to wild-type mice

• hepatic bile acid levels are 2x as high as in wild-type mice at 12 months of age

increased liver cholesterol level ( J:64792 )

• mutants on a 1% cholesterol diet show 1.4-fold greater hepatic cholesterol levels

increased liver triglyceride level ( J:64792 )

• mutants on a regular diet show 2.2-fold greater hepatic triglyceride levels

• mutants on a 1% cholesterol diet show 2.4-fold greater hepatic triglyceride levels

increased hepatocyte apoptosis ( J:121075 )

• mutants exhibit an increase in hepatocyte apoptosis as indicated by an increase in TUNEL staining; 3 month old mutants show a higher level of apoptosis than 12 month old mutants

increased hepatocyte proliferation ( J:121075 )

• BrdU labeling indicates increased hepatocyte proliferation at 3 months of age compared to wild-type mice; at 12 months of age, proliferation has decreased but is still significantly higher than in controls

abnormal liver morphology ( J:64792 )

• mutants on a 1% cholic acid diet exhibit liver lesions indicative of severe hepatotoxicity, with numerous vacuolated and necrotic cells

enlarged liver ( J:121075 )

• liver size, as a percentage of body weight, is higher than in wild-type mice at 12 months of age

increased liver cholesterol level ( J:64792 )

• mutants on a 1% cholesterol diet show 1.4-fold greater hepatic cholesterol levels

increased liver triglyceride level ( J:64792 )

• mutants on a regular diet show 2.2-fold greater hepatic triglyceride levels

• mutants on a 1% cholesterol diet show 2.4-fold greater hepatic triglyceride levels

hepatic steatosis ( J:64792 )

• mutants on a regular diet or a 1% cholesterol diet exhibit more lipid containing vacuoles in the liver than wild-type

increased liver tumor incidence ( J:121075 )

• 64% of mutants at 12 months of age display preneoplastic foci

• 38% total tumor incidence in 12 month old mutants; older mice were not analyzed for further tumor incidence

• both male and female mutants have liver lesions at 12 months of age; degenerative lesions consist of hypertrophic and eosinophilic hepatocytes accompanied by proliferating oval cells and lipid disposition

• 9% of mutants at 12 months of age develop mixed tumors consisting of hepatocellular carcinoma and hepatocholangiocellular carcinoma; mixed tumor involves a fibrous stroma and immune cell infiltrate, ductile formation and fibrosis

increased hepatocellular carcinoma incidence ( J:121075 )

• 6% of mutants at 12 months of age develop hepatocellular carcinoma

increased liver adenoma incidence ( J:121075 )

• 36% of mutants at 12 months of age develop hepatocellular adenomas