| Project/Area Number |
08458273
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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 |
Laboratory animal science
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| Research Institution | Gunma University |
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Principal Investigator |
IZUMI Tetsuro Department of Molecular Medicine, Institute for Molecular and Cellular Regulation, Gunma University, Associate Professor., 生体調節研究所, 助教授 (00212952)
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| Co-Investigator(Kenkyū-buntansha) |
TAKEDA Jun Department of Molecular Genetics, Institute for Molecular and Cellular Regulatio, 生体調節研究所, 教授 (40270855)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥6,800,000 (Direct Cost: ¥6,800,000)
Fiscal Year 1997: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1996: ¥3,800,000 (Direct Cost: ¥3,800,000)
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| Keywords | diabetes mellitus / obesity / polygenic disease / quantitative trait locus / insulin resistance / beta-cell dysfunction / animal models / QTLマッピング / 多因子遺伝性モデル動物 |
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| Research Abstract |
The molecular pathogenesis of diabetes remains poorly understood because of the genetic complexity of the disease. One possibly effective approach to elucidate the pathogenesis is to study an animal model with a similar phenotype. The TSOD (Tsumura, Suzuki, Obese Diabetes) mouse, a newly developed animal model, exhibits both diabetes and obesity with marked hyperinsulinemia and hypertrophy of the pancreatic islets, and might represent a common form of obese type 2 diabetes in humans. Phenotypic characterization revealed that the TSOD mouse had both insulin resistance and impaired glucose-stimulated insulin secretion. A comprehensive genetic dissection of diabetes and obesity has been performed using Fl and F2 progeny between the TSOD and control BALB/cA strains. A genome-wide screen for loci linked to glucose homeostasis and body weight allowed us to map three quantitative trait loci (QTLs) involved in this disorder. The major genetic determinant of blood glucose levels was identified on chromosome 11. Furthermore, two independent QTLs involved in controlling body weight were found on chromosomes 1 and 2. The QTh on chromosome 2 also affected insulin levels significantly. Each QTL has distinct effects on different traits and a different mode of inheritance. Our study indicates that hyperglycemia and obesity are clearly controlled by distinct combinations of genetic loci in this mouse model and provides insights into the genetic basis of common forms of human type 2 diabetes with obesity.
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