2003 Fiscal Year Final Research Report Summary
Identification of susceptibility gene of diabetes mellitus by QTL analysis in the genetic modified mice
| Project/Area Number |
13470227
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | The University of Tokushima |
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Principal Investigator |
ITAKURA Mitsuo The University of Tokushima, Institute for Genome Research, Division of Genetic Information, professor, ゲノム機能研究センター, 教授 (60134227)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAOKA Takashi The University of Tokushima, Institute for Genome Research, Division of Genetic Information, research associate, ゲノム機能研究センター, 助教授 (40263826)
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| Project Period (FY) |
2001 – 2003
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| Keywords | multifactorial disease / modifier gene for diabetes / type II diabetes / QTL analysis / db mice / susceptibility gene / animal model for diabetes / F2 intercross mice |
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| Research Abstract |
Diabetes is one of the typical "common diseases" and a major public health problem in Japan. Type 2 diabetes mellitus (T2D) results from the interaction between "genetic" and "environmental" factors. It is very important to identify the disease-susceptibility genes of diabetes. Mouse models of human diseases offer a powerful method to analyze human diseases. To identify the susceptibility genes of T2D, we performed genome-wide quantitative trait loci (QTL) analysis in 788 F_2 intercross generation between db mice carrying a mutation of leptin receptor (BKS-db/+m) with C3H/HeJ (C3H) mice. db mouse (BKS-db/db) having a mutation in the leptin receptor gene, is an animal model for T2D in humans
The phenotypes, including body weight, fasting blood glucose (BG) concentrations, fat weight, and intraperitoneal glucose tolerance test were determined. Correlation between genotypes with the whole genome 203 microsatellite markers and these quantitative phenotypes, were examined in a diabetic group including those homozygous for db (F_2-db/db) and a non-diabetic group including those heterozygous (F2 db/+m} and wild type (F_2-wild) for db. Vie found 18 QTLs (Lod Score >2.8 of suggestive value} for diabetes-related phenotypes including body weight, fat weight, and glucose tolerance. These loci also provide the susceptibility candidate regions to diabetes in humans. Production of the congenic mice is under way in our laboratory
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