Inactivation of CUG-BP1/CELF1 causes growth, viability, and spermatogenesis defects in mice
Inactivation of CUG-BP1/CELF1 causes growth, viability, and spermatogenesis defects in mice
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DOI：
10.1128/mcb.01009-06
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发表时间：
2007-02-01
影响因子：
5.3
通讯作者：
Paillard, Luc
中科院分区：
文献类型：
--
作者：
Kress, Chantal;Gautier-Courteille, Carole;Paillard, Luc
CUG-BP 1/CELF 1是一种多功能RNA结合蛋白，参与可变剪接和翻译的调节。为了阐明其在哺乳动物发育中的作用，我们生产了Cugbp 1基因通过同源重组失活的小鼠。这些Cugbp 1（-/-）小鼠是可以存活的，尽管它们中的很大一部分在生命的最初几天后没有存活下来。他们表现出生长迟缓，大多数Cugbp 1（-/-）男性和女性表现出受损的生育能力。对男性不育症进行了更彻底的调查。对Cugbp 1（-/-）雄性动物睾丸的组织学检查显示，在精子发生的第7步，精子细胞伸长开始之前，精子发生停滞，细胞凋亡增加。定量逆转录酶PCR分析显示，所有的生殖细胞标志物的测试，但不是Sertoli和Leydig标志物的减少，这表明生殖细胞数量的普遍减少。在野生型睾丸中，CUG-BP 1在从精原细胞到圆形精子细胞的生殖细胞中表达，也在支持细胞和间质细胞中表达。这些发现表明CUG-BP 1是完成精子发生所必需的。
CUG-BP1/CELF1 is a multifunctional RNA-binding protein involved in the regulation of alternative splicing and translation. To elucidate its role in mammalian development, we produced mice in which the Cugbp1 gene was inactivated by homologous recombination. These Cugbp1(-/-) mice were viable, although a significant portion of them did not survive after the first few days of life. They displayed growth retardation, and most Cugbp1(-/-) males and females exhibited impaired fertility. Male infertility was more thoroughly investigated. Histological examination of testes from Cugbp1(-/-) males showed an arrest of spermatogenesis that occurred at step 7 of spermiogenesis, before spermatid elongation begins, and an increased apoptosis. A quantitative reverse transcriptase PCR analysis showed a decrease of all the germ cell markers tested but not of Sertoli and Leydig markers, suggesting a general decrease in germ cell number. In wild-type testes, CUG-BP1 is expressed in germ cells from spermatogonia to round spermatids and also in Sertoli and Leydig cells. These findings demonstrate that CUG-BP1 is required for completion of spermatogenesis.