Aldh2^tm1.1Mak

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)