Zhou Yong-Xing, Zhao Mingrui, Li Dan, Shimazu Kazuhiro, Sakata Kazuko, Deng Chu-Xia, Lu Bai
Mammalian Genetics Section, National Institute of Diabetes and Digestive and Kidney Diseases/NIH, Bethesda, MD 20892, USA..
J Biol Chem. 2003 Oct 24;278(43):42313-20. doi: 10.1074/jbc.M308287200. Epub 2003 Aug 1.
Smad4 is a central mediator of TGF-beta signals, which are known to play essential roles in many biological processes. Using a Cre-loxP approach to overcome early embryonic lethality, we have studied functions of TGF-beta/Smad4 signals in the central nervous system (CNS). No obvious deficits were detected in mice carrying the targeted disruption of Smad4 in the CNS. The overall morphology of the hippocampus appeared normal. There was no change in the proliferation of neuronal precursor cells, nor in several forms of synaptic plasticity. In contrast, deletion of Smad4 resulted in a marked decrease in the number of cerebellar Purkinje cells and parvalbumin-positive interneurons. Accompanied by the abnormality in the cerebellum, mutant mice also exhibited significantly increased vertical activity. Thus, our study reveals an unexpected role for Smad4 in cerebellar development and in the control of motor function.
Smad4是转化生长因子β（TGF-β）信号的核心介质，已知该信号在许多生物学过程中发挥重要作用。我们采用Cre-loxP方法来克服早期胚胎致死性，研究了TGF-β/Smad4信号在中枢神经系统（CNS）中的功能。在中枢神经系统中携带Smad4靶向缺失的小鼠未检测到明显缺陷。海马体的整体形态看起来正常。神经元前体细胞的增殖以及几种形式的突触可塑性均未发生变化。相比之下，Smad4的缺失导致小脑浦肯野细胞和小白蛋白阳性中间神经元的数量显著减少。伴随着小脑的异常，突变小鼠的垂直活动也显著增加。因此，我们的研究揭示了Smad4在小脑发育和运动功能控制中的意外作用。
