Point mutation of aldehyde dehydrogenase-2 gene in mutant strains of Long-Evans rats.
Long-Evans Cinnamon (LEC) and Long-Evans Agouti (LEA) rats are mutant strains established from Long-Evans rats. LEC rats display hereditary hepatitis and spontaneous hepatocellular carcinoma, but LEA rats do not develop liver diseases. We previously demonstrated that LEC rats had an impairment of liver aldehyde dehydrogenase (ALDH) activities, and all LEC rats which were fed with a liquid diet containing 5% ethanol died within 2 weeks. In the present study, we also found that LEA rats could not metabolize ethanol and died after being fed the same diet. Remarkably, in the liver of LEA rats, low Km ALDH activities were suppressed as much as in LEC rats. These results suggested that both LEC and LEA rats have hereditary deficiencies in ALDH. Nucleotide sequence analysis of ALDH2 genes in both LEC and LEA rats demonstrated that the point mutation of the codon for residue 67 encoding Gln to Asp was observed; this was not so in either Long-Evans rats or Wistar rats. This mutation in ALDH2 genes may cause inactivation of ALDR activity in LEC and LEA rats.
Nakajima
M
M
Fourth Department of Internal Medicine, Sapporo Medical University School of Medicine, Chuo-ku, Japan.
Kato
J
J
Kohgo
Y
Y
Takeichi
N
N
Niitsu
T
T
D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D003062:Codon; D000431:Ethanol / Q000009:adverse effects / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D051381:Rats; D011922:Rats, Mutant Strains
D003062:Codon; D000431:Ethanol; D000444:Aldehyde Dehydrogenase