Phenotypes associated with this allele

• Allele Symbol: Cyp2b10^{tm1a(KOMP)Wtsi}
• Allele Name: targeted mutation 1a, Wellcome Trust Sanger Institute
• Allele ID: MGI:4364945
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Cyp2b10^tm1a(KOMP)Wtsi/Cyp2b10^tm1a(KOMP)Wtsi	C57BL/6N-Cyp2b10^tm1a(KOMP)Wtsi	MGI:7532771

Genotype
MGI:7532771

hm1

• Allelic Composition: Cyp2b10^{tm1a(KOMP)Wtsi}/Cyp2b10^{tm1a(KOMP)Wtsi}
• Genetic Background: C57BL/6N-Cyp2b10^{tm1a(KOMP)Wtsi}

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

liver/biliary system

increased susceptibility to alcohol-induced hepatic steatosis ( J:339440 )

• when chronically (8-week) EtOH-fed mice are given a single EtOH binge (E8G1), mice exhibit higher levels of liver steatosis, neutrophil infiltration and fibrosis than similarly treated wild-type controls

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:339440 )

N • after E8G1 (chronic-plus-single binge EtOH) or E8G3 (chronic-plus-three binges EtOH), mice show no significant differences in serum triglyceride or cholesterol levels relative to similarly treated wild-type controls

abnormal homeostasis ( J:339440 )

• after E8G1, several liver metabolites related to the gamma-glutamyl cycle and glutathione disposition are altered, including increases in 5-oxoproline (pyroglutamic acid/pyrrolidonecarboxylic acid), cysteinylglycine, glutathione and glutathione disulfide, and a reduction in L-glutamic acid; in addition, glucuronide metabolites ethyl glucuronide and thyroxine glucuronide are increased

abnormal lipid oxidation ( J:339440 )

• after E8G1, livers show increased 4-HNE (4-Hydroxynonenal) adducts, indicating increased levels of lipid peroxidation

• however, after E8G3, 4-HNE adducts are lower than post E8G1 and similar to those in E8G3 wild-type livers

abnormal blood homeostasis ( J:339440 )

• after E8G1, major alterations in serum metabolites include several carnitine metabolites that are mostly reduced; in addition, serum kynurenine is drastically decreased

increased circulating alanine transaminase level ( J:339440 )

• after E8G1, mice exhibit significantly higher serum ALT levels than similarly treated wild-type controls

• however, after E8G3, serum ALT levels are lower than post E8G1 and not significantly different from those in E8G3 wild-type controls

abnormal ethanol metabolism ( J:339440 )

• after E8G1 (chronic-plus-single binge EtOH) or E8G3 (chronic-plus-three binges EtOH), serum EtOH levels are significantly higher than in wild-type controls at 1 h after E8G1 or E8G3 (5 g/kg), indicating altered chronic-plus-binge EtOH clearance

• however, no differences in serum EtOH levels are observed at any time point after an acute EtOH binge (single dose of 5 g/kg) relative to wild-type controls

• in vitro, isolated liver microsomes treated with TCPOBOP (a Cyp2b10 inducer) or with TCPOBOP plus PPP (a CYP2b10 inhibitor) and challenged with EtOH show no alterations in EtOH oxidation to acetaldehyde, as observed in similarly treated wild-type microsomes

cellular

abnormal lipid oxidation ( J:339440 )

• after E8G1, livers show increased 4-HNE (4-Hydroxynonenal) adducts, indicating increased levels of lipid peroxidation

• however, after E8G3, 4-HNE adducts are lower than post E8G1 and similar to those in E8G3 wild-type livers