2013 Fiscal Year Final Research Report
A novel approach for identification of the genes responsible for hypertensive phenotype in SHRSP
| Project/Area Number |
24790846
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Kidney internal medicine
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| Research Institution | Shimane University |
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Principal Investigator |
OHARA Hiroki 島根大学, 医学部, 助教 (10609225)
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Keywords | 高血圧 / 疾患モデル / ストレス / コンジェニックラット |
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| Research Abstract |
Exaggerated sympathetic response to stress in the stroke-prone spontaneously hypertensive rat (SHRSP) have been implicated in the pathogenesis observed in this strain. Previously, by using a congenic strain constructed between SHRSP and the normotensive Wistar-Kyoto rat (WKY), we showed that a 1.8-Mbp region on chromosome 1 of SHRSP affects the sympathetic response to stress. In this study, subcongenic analyses further narrowed down the candidate region to a 1.2-Mbp fragment. Gene expression analysis and whole genome sequence analysis identified Stim1 as a strong candidate gene as a nonsense mutation was found in this gene of SHRSP. A western blot analysis confirmed a truncated form of STIM1 in SHRSP. In addition, the analysis revealed that the protein level of STIM1 in the brainstem of SHRSP was significantly lower when compared with WKY. Our results suggested that Stim1 is a strong candidate gene responsible for the exaggerated sympathetic response to stress in SHRSP.
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