Gab2 acts synergistically with Gab1 in the regulation of brain development and functions
作者单位：Institute of Molecular Pathology & Program in Molecular Cell BiologyDepartment of Basic Medical SciencesZhejiang University School of Medicine388 Yuhang Tang RdHangzhouChina310058
会议名称：《2010中国青年遗传学家论坛》
会议日期：2010年
学科分类：1002[医学-临床医学] 100203[医学-老年医学] 10[医学]
摘 要：In recent years,there has been considerable interest in genetic variants of the human GAB2 gene as a potential risk factor of Alzheimer’s disease,and this notion is supported by population-based genetic ***,the physiological role played by Gab2 in the brain remains *** findings of the present suggest that a complimentary mechanism of Gab 1 is responsible for normal neural functions and *** docking proteins GAB1 and GAB2 are strongly expressed in the brain belonging to the GAB adaptor family(GABs),which integrates multiple signals in response to various growth *** examined the role of GAB family proteins in the central nervous system (CNS) by generating embryonic brain-specific Gab1/Gab2 double knock-out mice (Nestin-Cre/Gab1F/FGab2N/N,DKOs).Compared to single GAB KO (Nestin-Cre/Gab1F/FGab2N/+,Gab1 KOs & Gab1F/FGab2N/N,Gab2 KOs) and control mice (Gab 1 F/FGab2N/+),DKO mice exhibited retarded growth with high postnatal *** noticed two major phenotypic abnormalities in the developmental brain of the DKO mice:(1) a remarkably reduced self-renewal capacity of neural stem/precursor cells(NSPCs) because of impaired EGF/bFGF-mediated ERK/STATs signaling and(2) progressive neuronal pathological alterations in the hippocampus,implying potential neural functional *** addition,animal studies were used to confirm the synergistic roles of GABs in maintaining multiple neural *** brain disruption in DKOs(Nestin-Cre/Gab lF/FGab2N/N) seems to make them susceptible to kainate-induced epilepsy and death after seizure,whereas mice with postnatal hippocampal deletion of GABs(CamKII-Cre/Gab1F/FGab2N/N) survive normally but display impaired fear conditioning function,implying the potential role of GABs in memory-learning *** together,this study is the first to use in vivo evidences to show the insufficient role of Gab2 in the brain,whereas the synergistic roles of GABs is required for neural developments an