Multidimensional analyses of the CDKL5, a causative gene for neurodevelopment disorders, by proteomic and LOF approaches
| Project/Area Number |
23500381
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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 |
Neuroscience in general
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Tanaka Teruyuki 東京大学, 医学(系)研究科(研究院), 准教授 (10246647)
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| Co-Investigator(Kenkyū-buntansha) |
天野 睦紀 名古屋大学, 医学(系)研究科(研究院), 准教授 (90304170)
水口 雅 東京大学, 医学(系)研究科(研究院), 教授 (20209753)
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| Co-Investigator(Renkei-kenkyūsha) |
KAIBUCHI Kozo 名古屋大学, 大学院医学系研究科, 教授 (00169377)
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| Project Period (FY) |
2011 – 2013
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 発達障害 / てんかん / シナプス / ノックアウトマウス / プロテオーム解析 / キナーゼ / 海馬 / レット症候群 / プロテオーム / 遺伝子改変マウス / 行動解析 / リン酸化 / 相互作用 / 情動障害 / 記憶障害 |
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| Outline of Final Research Achievements |
The Cyclin-dependent kinase-like 5 (CDKL5) gene encodes for a serine-threonine kinase sharing homology to Mitogen-activated kinases (MAPKs) and Cyclin-dependent kinases (CDKs). Recently, mutations in the CDKL5 gene have been identified in the patients with neurodevelopmental disorders associated with intractable epilepsies. However, neither its molecular functions or pathomechanisms caused by its mutations are largely unknown. Aiming to elucidate these problems, I have taken multidimensional strategies, combining an unbiased interactome approach and a targeted loss-of-function (LOF) approach. For the LOF approach, we have generated the Cdkl5 knockout mouse and identified various neurological abnormalities. For the interactome approach, we performed the yeast two-hybrid screening and proteomic screening, and identified several CDKL5 interacting proteins. The combination of these approaches suggested possible mechanisms of CDKL5 regulating neural functions during development.
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Report
(4 results)
Research Products
(16 results)
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[Presentation] Functional studies of the CDKL5, a causative gene of neurodevelopmental disorder, by interactome screening and loss-of-function analysis2013
Author(s)
Kosuke Okuda, Aya Watanabe, Shizuka Kobayashi, Toshiya Manabe, Keizo Takao, Tsuyoshi Miyakawa, Masahiro Fukaya, Hiroyuki Sakagami, Tomoki Nishioka, Mutsuki Amano, Kozo Kaibuchi, Masashi Mizuguchi, Teruyuki Tanaka
Organizer
第36回日本神経科学大会
Place of Presentation
京都市
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