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 no t 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 d ied 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. R emarkably, in the liver of LEA rats, low K-m ALDH activities were supp ressed as much as in LEC rats. These results suggested that both LEC a nd 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 ob served; this was not so in either Long-Evans rats or Wistar rats. This mutation in ALDH2 genes may cause inactivation of ALDH activity in LE C and LEA rats.