| Project/Area Number |
17K10068
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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 |
Pediatrics
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| Research Institution | National Center for Child Health and Development |
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Principal Investigator |
Fujiwara Shigeyoshi 国立研究開発法人国立成育医療研究センター, 免疫アレルギー・感染研究部, 特任研究員 (30173488)
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| Co-Investigator(Kenkyū-buntansha) |
中村 浩幸 国立研究開発法人国立成育医療研究センター, 免疫アレルギー・感染研究部, 室長 (70256866)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 先天性サイトメガロウイルス感染症 / サイトメガロウイルス / CMV / SLITRK6 / 難聴 / ヒトサイトメガロウイルス / 神経幹・前駆細胞 |
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| Outline of Final Research Achievements |
Cytomegalovirus (CMV) infection in pregnant women causes multiple organ damages in fetuses such as sensorineural hearing loss and neurodevelopmental impairment. To understand the molecular mechanism of CMV neuropathogenesis, we previously identified SLITRK6, a known causative gene for hereditary hearing loss, as a potentially important gene involved in CMV pathogenesis. To understand the relevance of SLITRK6 to CMV neuropathogenesis, we established human neural cells in which the expression of SLITRK6 was experimentally downregulated by shRNA or upregulated by SLITRK6 expression plasmid. Using the cells, we performed microarray analysis and identified cellular genes which may be regulated by SLITRK6. Further, murine cytomegalovirus (MCMV) was experimentally infected to mouse neural cells to analyze the effect of MCMV infection on mouse Slitrk6 expression. These experimental systems will be useful to understand the mechanism of CMV-induced neural damages through SLITRK6.
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| Academic Significance and Societal Importance of the Research Achievements |
先天性サイトメガロウイルス（CMV）感染は、難聴や精神発達遅滞などの神経・感覚器障害を合併する。本研究では、その発症メカニズムを理解することを目的として、CMV感染と遺伝性難聴の原因遺伝子として知られるSLITRK6との関連に着目し、神経系培養細胞を用いた新たな解析系を確立し解析を進めた。本研究で用いた実験系および得られた知見は、SLITRK6の神経系細胞における機能およびCMVによる難聴・神経障害発症に対するSLITRK6の関連性を明らかにする上で重要であり、CMV神経病原性の理解を今後深める上でも有用と考えられる。
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