All Phenotypes Cyp2c70<em1Utr> MGI Mouse

Phenotypes associated with this allele

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

mortality/aging

premature death ( J:302190 )

• unexpected death within a week of weaning (4 weeks of age) is seen in 20-25% of mice

• however, growth of surviving mice is good at least until 11 weeks of age

reproductive system

reduced fertility ( J:302190 )

• fertility is low

growth/size/body

increased liver weight ( J:302190 )

• liver weight is increased in males

homeostasis/metabolism

decreased intestinal cholesterol absorption ( J:302190 )

• intestinal cholesterol absorption, as estimated by serum sitosterol and campesterol, is reduced

increased circulating cholesterol level ( J:302190 )

• serum total cholesterol concentration is increased by 40% in males

• in females, total serum cholesterol concentration tends to be increased, but not significantly

• however, no change in serum and liver triglyceride concentrations are seen

increased circulating alanine transaminase level ( J:302190 )

• in males

increased circulating alkaline phosphatase level ( J:302190 )

• in males

abnormal bile salt homeostasis ( J:302190 )

• mice show complete replacement of muricholic acids (MCAs) by chenodeoxychoic acids (CDCAs) in both sexes

• hyocholic acid (HCA) pool is larger than in wild-type mice

• total bile acid pool is reduced by approximately 50% in both sexes

• hepatic bile acid content is elevated in males

• fecal bile acid concentration is decreased

• hepatic activity of key enzyme in bile acid biosynthesis is reduced, with CYP7A1 enzyme activity decreased by more than 50% in males and more than 80% in females, CYP8B1 activity decreased by approximately 93% in both sexes, and CYP7B1 enzyme activity is decreased by about 60% in males and about 50% in females

• however, CYP27A1 enzyme activity is not affected

decreased bile salt level ( J:302190 )

• total bile acid pool is reduced by approximately 50% in both sexes

decreased feces bile salt level ( J:302190 )

• fecal bile acid concentration is decreased

increased liver cholesterol level ( J:302190 )

• liver total cholesterol concentration is increased by 74% in males

abnormal enzyme/coenzyme activity ( J:302190 )

• CYP7A1 enzyme activity is decreased by more than 50% in males and more than 80% in females

• CYP8B1 activity is decreased by approximately 93% in both sexes

• CYP7B1 enzyme activity is decreased by about 60% in males and about 50% in females

• however, CYP27A1 enzyme activity is not affected

liver/biliary system

abnormal bile duct morphology ( J:302190 )

• males show diffuse bile ductular reaction in the liver and necrosis of hepatocytes (about 10%) with notable infiltration of lymphocytes and neutrophils, suggesting chronic hepatocyte damage and inflammation

liver inflammation ( J:302190 )

• males show notable infiltration of lymphocytes and neutrophils in the liver

abnormal liver morphology ( J:302190 )

• hepatic bile acid content is elevated in males

increased liver weight ( J:302190 )

• liver weight is increased in males

increased liver cholesterol level ( J:302190 )

• liver total cholesterol concentration is increased by 74% in males

hepatic necrosis ( J:302190 )

• males show necrosis of hepatocytes (about 10%)

digestive/alimentary system

decreased feces bile salt level ( J:302190 )

• fecal bile acid concentration is decreased

decreased intestinal cholesterol absorption ( J:302190 )

• intestinal cholesterol absorption, as estimated by serum sitosterol and campesterol, is reduced

endocrine/exocrine glands

abnormal bile duct morphology ( J:302190 )

immune system

liver inflammation ( J:302190 )

• males show notable infiltration of lymphocytes and neutrophils in the liver

Allelic Composition	Cyp2a12^em1Utr/Cyp2a12^em1Utr Cyp2c70^em1Utr/Cyp2c70^em1Utr
Genetic Background	C57BL/6J-Cyp2a12^em1Utr Cyp2c70^em1Utr

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cyp2a12^em1Utr mutation (0 available); any Cyp2a12 mutation (36 available)
Cyp2c70^em1Utr mutation (0 available); any Cyp2c70 mutation (38 available)

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

mortality/aging

premature death ( J:302190 )

• unexpected death within a week of weaning (4 weeks of age) is seen in 20-25% of mice

• however, growth of surviving mice is good at least until 11 weeks of age

reproductive system

reduced fertility ( J:302190 )

• fertility is slightly lower

growth/size/body

increased liver weight ( J:302190 )

• liver weight is increased in both sexes

homeostasis/metabolism

decreased intestinal cholesterol absorption ( J:302190 )

• intestinal cholesterol absorption, as estimated by serum sitosterol and campesterol, is reduced

increased circulating alanine transaminase level ( J:302190 )

• in males

increased circulating alkaline phosphatase level ( J:302190 )

• in males

abnormal bile salt homeostasis ( J:302190 )

• deoxycholic acids (DCAs), chenodeoxycholic acids (CDCAs), and lithocholic acids (LCAS) are increased in the tissues

• total bile acid pool is reduced by approximately 50% in both sexes

• hepatic bile acid content is elevated in females

• fecal bile acid concentration is decreased

• hepatic activity of key enzyme in bile acid biosynthesis is reduced, with CYP7A1 enzyme activity decreased by more than 50% in males and more than 80% in females and CYP7B1 enzyme activity decreased by about 60% in males and about 50% in females

• however, CYP8B1 and CYP27A1 enzyme activity are not affected

decreased bile salt level ( J:302190 )

• total bile acid pool is reduced by approximately 50% in both sexes

decreased feces bile salt level ( J:302190 )

• fecal bile acid concentration is decreased

abnormal cholesterol homeostasis ( J:302190 )

• serum 4beta-hydroxycholesterol is elevated

• liver desmosterol level in males is increased

decreased circulating cholesterol level ( J:302190 )

• serum total cholesterol concentration is decreased by 24% in males

• however, liver total cholesterol concentrations are unchanged and no change in serum and liver triglyceride concentrations are seen

abnormal enzyme/coenzyme activity ( J:302190 )

• taurodeoxycholic acid (TDCA) 7alpha-hyddroxylase activity in the liver is reduced to approximately 10% of wild-type levels

• taurochenodeoxycholic acid (TCDCA) 6beta-hydroxylase activity is almost absent in the liver

• CYP7A1 enzyme activity is decreased by more than 50% in males and more than 80% in females

• CYP7B1 enzyme activity is decreased by about 60% in males and about 50% in females

• however, CYP8B1 and CYP27A1 enzyme activity are not affected

liver/biliary system

abnormal bile duct morphology ( J:302190 )

• males show a slight bile ductular reaction in the liver, but necrosis of hepatocytes is not seen

abnormal liver morphology ( J:302190 )

• hepatic bile acid content is elevated in females

• liver desmosterol level in males is increased

increased liver weight ( J:302190 )

• liver weight is increased in both sexes

abnormal bile composition ( J:302190 )

• biliary proportions of cholesterol and phospholipid are elevated with a decrease in the bile acid pool in males

digestive/alimentary system

decreased feces bile salt level ( J:302190 )

• fecal bile acid concentration is decreased

decreased intestinal cholesterol absorption ( J:302190 )

• intestinal cholesterol absorption, as estimated by serum sitosterol and campesterol, is reduced

endocrine/exocrine glands

abnormal bile duct morphology ( J:302190 )

• males show a slight bile ductular reaction in the liver, but necrosis of hepatocytes is not seen

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