1995 Fiscal Year Final Research Report Summary
Analysis of gene abnormalities in newly found rats with congenital defect of alcohol metabolism.
| Project/Area Number |
06670568
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Gastroenterology
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| Research Institution | Asahikawa Medical College (1995)
Sapporo Medical University (1994) |
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Principal Investigator |
KOHGO Yutaka Asahikawa Medical College, Internal Medicine, Professor, 医学部, 教授 (10133183)
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| Co-Investigator(Kenkyū-buntansha) |
ONO Minoru Asahikawa Medical College, Internal Medicine, Lecturer, 医学部, 助手 (60185650)
KATO Junji Sapporo Medical University, Internal Medicine, Assistant Professor, 医学部, 講師 (20244345)
NEDA Hiroshi Sapporo Medical University, Internal Medicine, Assistant Professor, 医学部, 講師 (80237809)
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| Project Period (FY) |
1994 – 1995
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| Keywords | LEC Rats / LEA Rats / Class IADH Gene / ALDH2 Gene |
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| Research Abstract |
Long Evans Cinamon (LEC) and Long Evans Agouti (LEA) rats are mutant strains established from Long Evans rats. LEC rats display hereditary hepatitis and spontaneous hepatocellular carcinoma. We preveously found that both LEA and LEC rats fed with liquid diet containing 5% ethanol died within 2 weeks owing to acute ethanol intoxication. In the present study, the molecular abnormalities of ethanol metabolism on these strains were elucidated. Enzymatic activities of both alcohol dehydrogenase (ADH) and acetaldehyde deheydrogenase (ALDH) were decreased at the level of 60-75% of the control Wistar rats. Nucleotide sequence analysis of both LEC and LEA rat liver ALDH RNA (exon 3 of ALDH-2) showed that there was a point mutation ; CAG to CGG at codon 67, indicating the presence of variant low Km ALDH as seen in human oriental people. In addition to ALDH point mutation, ADH gene also showed an abnormality in the first intron of class 1 ADH gene. The sequence length of TG repeat was 98 base pairs, while that of control Wistar rat was 80 base pairs. This result suggests that the insertion of TG repeat was present in LEC rat and may be responsible for the reduction of transcriptional efficiency of ADH gene. In contrast, by Western blot analysis, cytochrome P450 expression 2E1 (MEOS activity) was induced 8 times higher by ethanol feeding in LEC rat, which is normal response.
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