Takagi Tsuyoshi, Jin Wanzhu, Taya Kazuyoshi, Watanabe Gen, Mori Kensaku, Ishii Shunsuke
Laboratory of Molecular Genetics, RIKEN Tsukuba Institute, 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan.
Brain Res. 2006 Sep 7;1108(1):88-97. doi: 10.1016/j.brainres.2006.06.018. Epub 2006 Jul 11.
The bone morphogenetic protein (BMP)/transforming growth factor-beta (TGF-beta)/activin superfamily regulates development of the nervous system during embryogenesis and is also suggested to be involved in adult brain function. However, how BMP/TGF-beta/activin signals modulate neuronal function remains unknown. Schnurri is a transcription factor that contains two metal finger regions. Mammalian Shn-2 enters the nucleus from the cytoplasm in response to BMP-2 stimulation and plays an important role in BMP-dependent adipogenesis. To investigate whether mammalian Shn plays a role in adult brain function, we examined the behaviors of mutant mice lacking Shn-2 (Shn-2(-/-)). Shn-2(-/-) mice exhibited hypersensitivity to stress accompanied by anxiety-like behavior. Consistent with this, stress-induced corticosterone levels were significantly higher in Shn-2(-/-) mice compared to wild-type controls. Interestingly, Shn-2(-/-) mice were more active than wild-type mice in a familiar environment. The basal and stress-induced expression levels of the immediate early genes, including c-Fos, were decreased in Shn-2(-/-) mice compared to wild-type mice. Thus, Shn-2 plays a critical role in locomotion and anxiety-like behavior.
骨形态发生蛋白（BMP）/转化生长因子-β（TGF-β）/激活素超家族在胚胎发育过程中调节神经系统的发育，并且也被认为参与成体脑功能。然而，BMP/TGF-β/激活素信号如何调节神经元功能仍不清楚。Schnurri是一种含有两个金属指区域的转录因子。哺乳动物的Shn-2在受到BMP-2刺激后从细胞质进入细胞核，并在BMP依赖的脂肪生成中起重要作用。为了研究哺乳动物的Shn是否在成体脑功能中起作用，我们检测了缺乏Shn-2（Shn-2(-/-)）的突变小鼠的行为。Shn-2(-/-)小鼠表现出对应激的超敏反应并伴有焦虑样行为。与此一致的是，与野生型对照相比，Shn-2(-/-)小鼠应激诱导的皮质酮水平显著更高。有趣的是，在熟悉的环境中，Shn-2(-/-)小鼠比野生型小鼠更活跃。与野生型小鼠相比，Shn-2(-/-)小鼠中包括c-Fos在内的即刻早期基因的基础表达水平和应激诱导表达水平均降低。因此，Shn-2在运动和焦虑样行为中起关键作用。
