Smad2 Protein Disruption in the Central Nervous System Leads to Aberrant Cerebellar Development and Early Postnatal Ataxia in Mice*
Smad2 Protein Disruption in the Central Nervous System Leads to Aberrant Cerebellar Development and Early Postnatal Ataxia in Mice*
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DOI：
10.1074/jbc.m111.223271
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发表时间：
2011-04
期刊：
影响因子：
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通讯作者：
Lixiang Wang;M. Nomura;Yutaka Goto;Kimitaka Tanaka;R. Sakamoto;Ichiro Abe;S. Sakamoto;Atsushi Shibata;Patricio L M Enciso;M. Adachi;K. Ohnaka;H. Kawate;R. Takayanagi
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文献类型：
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作者：
Lixiang Wang;M. Nomura;Yutaka Goto;Kimitaka Tanaka;R. Sakamoto;Ichiro Abe;S. Sakamoto;Atsushi Shibata;Patricio L M Enciso;M. Adachi;K. Ohnaka;H. Kawate;R. Takayanagi
Smad2是转化生长因子-β信号的关键介体，已知在各种细胞类型的广泛生物学过程中发挥重要作用。然而，它在中枢神经系统发展中的作用在很大程度上是未知的。采用Cre-loxP方法建立中枢Smad2缺失小鼠(Smad2-CNS-KO)。这些小鼠从出生后早期就表现出运动协调的行为异常，并在大约3周大时死亡，这表明严重的小脑功能障碍。大体观察发现，Smad2-CNS-KO小叶在小叶IX和X处有异常的叶状突起。进一步的分析发现，凋亡细胞死亡增加，颗粒细胞迁移和成熟延迟，浦肯野细胞的树突分枝迟缓。这些发现表明Smad2在小脑发育和运动功能控制中起着关键作用。
Smad2 is a critical mediator of TGF-β signals that are known to play an important role in a wide range of biological processes in various cell types. Its role in the development of the CNS, however, is largely unknown. Mice lacking Smad2 in the CNS (Smad2-CNS-KO) were generated by a Cre-loxP approach. These mice exhibited behavioral abnormalities in motor coordination from an early postnatal stage and mortality at approximately 3 weeks of age, suggestive of severe cerebellar dysfunction. Gross observation of Smad2-CNS-KO cerebella demonstrated aberrant foliations in lobule IX and X. Further analyses revealed increased apoptotic cell death, delayed migration and maturation of granule cells, and retardation of dendritic arborization of Purkinje cells. These findings indicate that Smad2 plays a key role in cerebellar development and motor function control.