Phenotypes Associated with This Genotype

Genotype
MGI:5789791

• Allelic Composition: Aldh2^tm1.1Mak/Aldh2^tm1.1Mak
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6J

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

Increased sensitivity of heterozygous and homozgyous Aldh2^tm1.1Mak mice to damage induced by chronic ethanol challenge

homeostasis/metabolism

abnormal enzyme/coenzyme activity ( J:223796 )

• after 8 months of diethylnitrosamine (DEN) treatment, homozygotes show significantly higher serum alanine transaminase (ALT) activity than DEN-treated wild-type controls, indicating severe liver injury

abnormal ethanol metabolism ( J:223796 )

• in culture, primary hepatocytes isolated from homozygous mice fail to clear [¹³C]acetaldehyde (ACE), a toxic intermediate product from ethanol metabolism, unlike wild-type controls

• homozygotes display slower ACE clearance after exposure to low-dose ethanol (2 g/kg) and fail to clear serum ACE after intermediate- (4 g/kg) or high-dose ethanol challenge (8 g/kg), unlike wild-type controls

increased incidence of tumors by chemical induction ( J:223796 )

• after 8 months of DEN treatment, homozygotes show a markedly greater number and larger volume of hepatocellular carcinomas than DEN-treated wild-type controls

• liver histology indicates more focal hepatic lesions while phospho-H2AX staining shows a substantially higher degree of DNA damage compared to DEN-treated wild-type controls

behavior/neurological

enhanced behavioral response to alcohol ( J:223796 )

• after 4 g/kg ethanol challenge, homozygotes display a marked increase in behavioral scores including severe ataxia compared to wild-type controls

• after 8 g/kg ethanol challenge, homozygotes show severe behavioral abnormalities including loss of righting reflex compared to wild-type controls

mortality/aging

increased susceptibility to induced morbidity/mortality ( J:223796 )

• after acute ethanol challenge with 8 g/kg (lethal dose), but not 2 or 4 g/kg, homozygotes display a marked reduction in survival rate compared to similarly treated wild-type controls

• after chronic ethanol challenge with 4 g/kg ethanol for 6 weeks, homozygotes display markedly reduced survival starting at 2 weeks, unlike wild-type controls

growth/size/body

decreased body weight ( J:223796 )

• after chronic ethanol challenge with 4 g/kg ethanol for 6 weeks, homozygotes show a marked reduction in body weight compared to wild-type controls

cellular

increased hepatocyte apoptosis ( J:223796 )

• after chronic ethanol challenge with 4 g/kg ethanol for 6 weeks, homozygotes display increased hepatocyte apoptosis, as shown by histology and cleaved caspase 3 staining

• however, no inflammatory or necrotic changes are observed in the esophagus or stomach after chronic ethanol challenge

hematopoietic system

decreased leukocyte cell number ( J:223796 )

• after chronic ethanol challenge with 4 g/kg ethanol for 6 weeks, homozygotes show a severe reduction in white cell count compared to wild-type controls

liver/biliary system

increased hepatocyte apoptosis ( J:223796 )

• after chronic ethanol challenge with 4 g/kg ethanol for 6 weeks, homozygotes display increased hepatocyte apoptosis, as shown by histology and cleaved caspase 3 staining

• however, no inflammatory or necrotic changes are observed in the esophagus or stomach after chronic ethanol challenge

neoplasm

increased incidence of tumors by chemical induction ( J:223796 )

• after 8 months of DEN treatment, homozygotes show a markedly greater number and larger volume of hepatocellular carcinomas than DEN-treated wild-type controls

• liver histology indicates more focal hepatic lesions while phospho-H2AX staining shows a substantially higher degree of DNA damage compared to DEN-treated wild-type controls

decreased tumor latency ( J:223796 )

• after 8 months of DEN treatment, homozygotes display accelerated development of hepatocellular carcinoma compared to DEN-treated wild-type controls

immune system

decreased leukocyte cell number ( J:223796 )

• after chronic ethanol challenge with 4 g/kg ethanol for 6 weeks, homozygotes show a severe reduction in white cell count compared to wild-type controls

pigmentation

hyperpigmentation ( J:223796 )

• after chronic ethanol challenge with 4 g/kg ethanol for 6 weeks, homozygotes display hyperpigmentation of paw skin, unlike wild-type controls