2016 Fiscal Year Final Research Report
Effect of type 2 diabetes susceptibility gene Kcnq1 gene region on pancreatic beta cells
| Project/Area Number |
26461382
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Endocrinology
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| Research Institution | Kobe University |
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Principal Investigator |
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Keywords | 膵β細胞 / 2型糖尿病感受性遺伝子 / エピジェネティクス |
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| Outline of Final Research Achievements |
Numerous susceptibility genes for type 2 diabetes, including KCNQ1, have been identified in humans by genome-wide analyses and other studies. Experiments with genetically modified mice have also implicated various genes in the pathogenesis of diabetes. However, possible parent-of-origin effects for diabetes susceptibility alleles on disease onset have remained unclear. Here, we show that a mutation at the Kcnq1 locus reduces pancreatic β cell mass in mice via epigenetic modulation only when it is paternally inherited. The noncoding RNA Kcnq1ot1 is expressed from the Kcnq1 locus and regulates the expression of neighboring genes on the paternal allele. We found that disruption of Kcnq1 results in reduced Kcnq1ot1 expression and increased Cdkn1c expression, an imprinted gene encoding a cell cycle inhibitor, only when the mutation is on the paternal allele. Furthermore, histone modification of the Cdkn1c promoter in pancreatic islets was found to contribute to this phenomenon.
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| Free Research Field |
糖尿病学
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