Multidimensional analyses of the CDKL5, a causative gene for neurodevelopment disorders, by proteomic and LOF approaches

2013 Fiscal Year Final Research Report

• Project/Area Number: 23500381
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neuroscience in general
• Research Institution: The University of Tokyo
• Principal Investigator: Tanaka Teruyuki 東京大学, 医学(系)研究科(研究院), 准教授 (10246647)
• 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)
• Co-Investigator(Renkei-kenkyūsha): KAIBUCHI Kozo 名古屋大学, 大学院医学系研究科, 教授 (00169377)
• Project Period (FY): 2011 – 2013
• 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

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.

Free Research Field

総合領域