Gene knockout analysis of two γ-tubulin isoforms in mice
Gene knockout analysis of two γ-tubulin isoforms in mice
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DOI：
10.1016/j.ydbio.2005.03.031
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发表时间：
2005-06-15
影响因子：
2.7
通讯作者：
Tsukita, S
中科院分区：
文献类型：
--
作者：
Yuba-Kubo, A;Kubo, A;Tsukita, S
γ-微管蛋白调节微管的成核，但对其在体内的功能的了解仍不完整。在这里，我们报告了两种密切相关的微管蛋白亚型TUBG1和TUBG2在小鼠中的鉴定，以及TUBG1和TUBG2缺陷小鼠的产生。TUBG1普遍表达，而TUBG2主要在大脑中检测到。TUBG1(-/-)缺陷(Tubg1(-/-))胚胎的发育停滞于桑椹/囊胚阶段，原因是有丝分裂停止：有丝分裂纺锤体高度紊乱，排列紊乱的纺锤体显示出一个或两个被浓缩的染色体包围的极状MTS焦点。TUBG2在胚泡中有表达，但不能挽救TUBG1的缺失。相比之下，TUBG2缺陷(Tubg2(-/-))小鼠出生、生长和杂交正常。在野生型小鼠的脑中，TUBG2的表达与TUBG1的表达大致相同，但在Tubg2(-/-)脑中没有发现组织学异常。这些发现表明，TUBG1和TUBG2在体内的功能并不相同，TUBG1对应于传统的伽马微管蛋白，TUBG2在大脑中可能具有一些未知的功能。(C)2005 Elsevier Inc.保留所有权利。
gamma-Tubulin regulates the nucleation of microtubules, but knowledge of its functions in vivo is still fragmentary. Here, we report the identification of two closely related gamma-tubulin isoforms, TUBG1 and TUBG2, in mice, and the generation of TUBG1- and TUBG2-deficient mice. TUBG1 was expressed ubiquitously, whereas TUBG2 was primarily detected in the brain. The development of TUBG1-deficient (Tubg1(-/-)) embryos stopped at the morula/blastocyst stages due to a characteristic mitotic arrest: the mitotic spindle was highly disorganized, and disorganized spindles showed one or two pole-like foci of bundled MTs that were surrounded by condensed chromosomes. TUBG2 was expressed in blastocysts, but could not rescue the TUBG1 deficiency. By contrast, TUBG2-deficient (Tubg2(-/-)) mice were born, grew, and intercrossed normally. In the brain of wild-type mice, TUBG2 was expressed in approximately the same amount as TUBG1, but no histological abnormalities were found in the Tubg2(-/-) brain. These findings indicated that TUBG1 and TUBG2 are not functionally equivalent in vivo, that TUBG1 corresponds to conventional gamma-tubulin, and that TUBG2 may have some unidentified function in the brain. (c) 2005 Elsevier Inc. All rights reserved.