Aldh2^tm1.1Mak
Targeted Allele Detail

Summary

• Symbol: Aldh2^tm1.1Mak
• Name: aldehyde dehydrogenase 2, mitochondrial; targeted mutation 1.1, Tak Mak
• MGI ID: MGI:5701667
• Synonyms: Aldh2^E487K
• Gene: Aldh2 Location: Chr5:121704090-121731887 bp, - strand Genetic Position: Chr5, 61.86 cM, cytoband F-G1
• Alliance: Aldh2^tm1.1Mak page

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

Show the 3 phenotype image(s) involving this allele.

Mutation origin

• Germline Transmission: Earliest citation of germline transmission: J:223796
• Parent Cell Line: Not Specified (ES Cell)
• Strain of Origin: 129S6/SvEvTac

Mutation description

Allele Type: Targeted (Dominant negative, Humanized sequence) Mutations: Insertion, Single point mutation Mutation details: Exon 12 was replaced with a floxed neomycin resistance cassette and a modified exon 12 in which a point mutation (G to A) results in the amino acid substitution of lysine for glutamic acid at position 487 (E487K). Cre-mediated recombination removed the selection cassette. The mutation reduces total liver ALDH2 protein levels via a dominant-negative effect on protein stability. Primary hepatocytes isolated from heterozygous mutants retain only 44% of ALDH2 enzymatic activity while homozygous mutant hepatocytes produce hardly detectable ALDH2 activity. Heterozygous mutant mice show an 85% decrease in liver ALDH2 protein whereas homozygotes display a nearly complete loss of ALDH2 protein. (J:223796)

Generation of the Aldh2^tm1.1Mak allele

Expression

In Structures Affected by this Mutation:

1 anatomical structure(s)

Tumor Data

List all tumor models in MMHCdb carrying Aldh2^tm1.1Mak

Find Mice (IMSR)

• Mouse strains and cell lines available from the International Mouse Strain Resource (IMSR)
• Carrying this Mutation: Mouse Strains: 0 strains available Cell Lines: 0 lines available
• Carrying any Aldh2 Mutation: 35 strains or lines available

References

• Original: J:223796 Jin S, et al., ALDH2(E487K) mutation increases protein turnover and promotes murine hepatocarcinogenesis. Proc Natl Acad Sci U S A. 2015 Jul 21;112(29):9088-93
• All: 2 reference(s)