| Co-Investigator(Kenkyū-buntansha) |
MAKINO Susumu Shionogi Laboratories AC Center, Head, ACセンター, センター長(研究職)
MIYAZAKI Jyun-ichi Osaka University Graduate School of Medicne, Professor, 医学研究科, 教授 (10200156)
FUJISAWA Tomomi Osaka University Graduate School of Medicne, Assistant Professor, 医学研究科, 助手 (10324766)
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| Research Abstract |
Multifactorial diseases such as diabetes and hypertension are caused by complex interaction of genetic and environmental factors. Genetic factor consists of multiple susceptible genes. The effect of each gene to overall phenotype is relatively small, making the identification and functional analysis of susceptibility genes for multifactorial diseases in humans difficult. To overcome this, we used inbred animal models for multifactorial diseases, in which genetic background is homogeneous and environmental factors can easily be controlled, and genetic and functional analyses were performed, and information generated from studies in these models were applied for human studies.
In NOD mice, an animal model for type 1 diabetes, a second component of MHC-linked susceptibility (Idd16) has been mapped to the region adjacent to, but distinct from class II MHC(Idd1), and candidate variants have been identified in promoter region of Tnf, encoding cytokine tumor necrosis factor. By ancestral haplotype congenic mapping, sequence variants in I12 and I121 have been shown to be strong candidates for non-MHC gene, Idd3. In NSY mice, an animal model for type 2 diabetes, three major susceptibility genes (Nidd1-3) have been mapped to chromosomes 11, 14 and 6, consomic strains possessing each of these chromosome have been produced and significant differences in phenotypes as compared with control strain have been shown, indicating the power of our strategy in genetic dissection of complex traits.
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