2011 Fiscal Year Final Research Report
Investigation of pathogenic mechanism of diabetes using novel mutant mice presenting with beta-cell dysfunction
| Project/Area Number |
21500394
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | The Institute of Physical and Chemical Research |
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Principal Investigator |
INOUE Maki 独立行政法人理化学研究所, 疾患モデル評価研究開発チーム, 開発研究員 (90321728)
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| Project Period (FY) |
2009 – 2011
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| Keywords | 糖尿病 / モデルマウス / 突然変異 / β細胞 / 原因遺伝子 / 遺伝的背景 / インスリン分泌 / ENU |
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| Research Abstract |
N-ethyl-N-nitrosourea(ENU) is an effective chemical mutagen that mainly introduces single base pair changes. In RKEN ENU mutagenesis project, we have established a severely diabetic mutant line presenting with severe beta-cell dysfunction. Through mapping analyses and sequencing of all exons in the fine-mapped region, we identified single missense mutation(N425K) in Srpr gene. Srpr is a key regulator of nascent chain transportation in endoplasmic reticulum(ER). Out results firstly show that dysfunction of ER export can lead to destruction of insulin-producing beta cells and pathogenesis of diabetes.
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