Kismet/CHD7 regulates axon morphology, memory and locomotion in a Drosophila model of CHARGE syndrome
Kismet/CHD7 regulates axon morphology, memory and locomotion in a Drosophila model of CHARGE syndrome
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DOI：
10.1093/hmg/ddq348
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发表时间：
2010-11-01
影响因子：
3.5
通讯作者：
Marenda, Daniel R.
中科院分区：
文献类型：
--
作者：
Melicharek, David J.;Ramirez, Laura C.;Marenda, Daniel R.
CHARGE综合征（CS，OMIM #214800）是一种罕见的常染色体显性遗传病，其中三分之二是由Chd7基因的单倍不足引起的。在这里，我们表明，果蝇同源的Chd7，kismet，需要适当的轴突修剪，指导和扩展在发展中的苍蝇的中枢神经系统。除了神经解剖学缺陷外，kismet表达减少的果蝇还表现出记忆和运动功能缺陷，表型与CS患者中观察到的症状一致。我们认为，这种疾病模型的分析可以补充和扩大对这种疾病的现有研究，允许更好地了解kismet在神经发育中的作用，和Chd7在CS发病机制。
CHARGE syndrome (CS, OMIM #214800) is a rare, autosomal dominant disorder, two-thirds of which are caused by haplo-insufficiency in the Chd7 gene. Here, we show that the Drosophila homolog of Chd7, kismet, is required for proper axonal pruning, guidance and extension in the developing fly's central nervous system. In addition to defects in neuroanatomy, flies with reduced kismet expression show defects in memory and motor function, phenotypes consistent with symptoms observed in CS patients. We suggest that the analysis of this disease model can complement and expand upon the existing studies for this disease, allowing a better understanding of the role of kismet in neural developmental, and Chd7 in CS pathogenesis.