Phenotypes associated with this allele

• Allele Symbol: Cyp2a12^em1Utr
• Allele Name: endonuclease-mediated mutation 1, University of Tsukuba Laboratory Animal Resource Center
• Allele ID: MGI:7643808
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Cyp2a12^em1Utr/Cyp2a12^em1Utr	C57BL/6J-Cyp2a12^em1Utr	MGI:7643811
cx2	Cyp2a12^em1Utr/Cyp2a12^em1Utr Cyp2c70^em1Utr/Cyp2c70^em1Utr	C57BL/6J-Cyp2a12^em1Utr Cyp2c70^em1Utr	MGI:7643815

Genotype
MGI:7643811

hm1

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

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

homeostasis/metabolism

decreased intestinal cholesterol absorption ( J:302190 )

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

abnormal bile salt homeostasis ( J:302190 )

• mice show accumulation of deoxycholic acids (DCAs)

• however, total bile acid pool size is not altered

abnormal enzyme/coenzyme activity ( J:302190 )

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

digestive/alimentary system

decreased intestinal cholesterol absorption ( J:302190 )

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

Genotype
MGI:7643815

cx2

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

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