Expression of the human TSPY gene in the brains of transgenic mice suggests a potential role of this Y chromosome gene in neural functions
Expression of the human TSPY gene in the brains of transgenic mice suggests a potential role of this Y chromosome gene in neural functions
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DOI：
10.1016/j.jgg.2011.04.002
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发表时间：
2011-05-01
影响因子：
5.9
通讯作者：
Lau, Yun-Fai Chris
中科院分区：
文献类型：
--
作者：
Kido, Tatsuo;Schubert, Stephanie;Lau, Yun-Fai Chris
睾丸特异性蛋白Y编码（TSPY）是TSPY/SET/NAP1超家族的成员，编码于Y染色体上的性腺母细胞瘤位点。TSPY具有高度保守的SET/ nap -结构域，负责TSPY/SET/NAP1蛋白之间的蛋白-蛋白相互作用。到目前为止，积累的数据支持TSPY作为性腺母细胞瘤基因参与生殖细胞肿瘤发生的作用。作为TSPY的x染色体同源物，TSPX在胎儿和成人阶段的各种组织中都有表达，包括大脑，并能与多结构域适配蛋白CASK相互作用，从而影响CASK在大脑和其他神经组织中的突触和转录功能以及发育调节。与TSPX类似，我们发现TSPY可以在培养细胞中与CASK的SET/ nap结构域相互作用。含有人TSPY基因及其侧链的转基因小鼠在睾丸和大脑中均有特异性表达。人类TSPY基因的神经表达模式与内源性小鼠Cask和Tspx基因的神经表达模式重叠。与TSPX类似，TSPY在大脑神经元轴突纤维中与CASK共定位，提示TSPY在神经系统发育和/或生理上的潜在作用。
The testis specific protein Y-encoded (TSPY) is a member of TSPY/SET/NAP1 superfamily, encoded within the gonadoblastoma locus on the Y chromosome. TSPY shares a highly conserved SET/NAP-domain responsible for proteine-protein interaction among TSPY/SET/NAP1 proteins. Accumulating data, so far, support the role of TSPY as the gonadoblastoma gene, involved in germ cell tumorigenesis. The X-chromosome homolog of TSPY, TSPX is expressed in various tissues at both fetal and adult stages, including the brain, and is capable of interacting with the multi-domain adapter protein CASK, thereby influencing the synaptic and transcriptional functions and developmental regulation of CASK in the brain and other neural tissues. Similar to TSPX, we demonstrated that TSPY could interact with CASK at its SET/NAP-domain in cultured cells. Transgenic mice harboring a human TSPY gene and flanking sequences showed specific expression of the human TSPY transgene in both testis and brain. The neural expression pattern of the human TSPY gene overlapped with those of the endogenous mouse Cask and Tspx gene. Similarly with TSPX, TSPY was co-localized with CASK in neuronal axon fibers in the brain, suggesting a potential role(s) of TSPY in development and/or physiology of the nervous system.