2016 Fiscal Year Final Research Report
A new pathogenesis of myelin-related disorders: a dysfunction of small RNA import into mitochondria
| Project/Area Number |
15K19597
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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 |
Pediatrics
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Project Period (FY) |
2015-04-01 – 2017-03-31
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| Keywords | 髄鞘化 / ミトコンドリア / 低分子RNA |
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| Outline of Final Research Achievements |
Recent studies suggest that impaired transcription or mitochondrial translation of small RNAs can cause abnormal myelination. We identified two siblings with "gene X" mutations who presented delayed myelination as well as mitochondrial dysfunction. The protein X facilitates the import of small RNAs into mitochondria. In this study, analyses of skin fibroblasts from the patient showed that import of the small RNA RNase P into mitochondria was impaired. Exogenous expression of wild-type PNPT1, but not mutants, rescued ATP production in patient skin fibroblasts, suggesting the pathogenicity of the identified mutations. We also generated mice carrying mutations in gene X. The first line of the mice results in embryonic lethal. We found no gene X mutations in 20 patients with dysmyelination.
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| Free Research Field |
小児神経学
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