CIB1 is essential for mouse spermatogenesis
CIB1 is essential for mouse spermatogenesis
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DOI：
10.1128/mcb.01488-06
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发表时间：
2006-11-01
影响因子：
5.3
通讯作者：
Parise, Leslie V.
中科院分区：
文献类型：
--
作者：
Yuan, Weiping;Leisner, Tina M.;Parise, Leslie V.
CIB1是一种22 kda的钙结合调节蛋白，与钙调蛋白和钙调磷酸酶b具有相似的50%的同源性。CIB1在不同组织中广泛表达并结合许多效应器，如整合素α IIb、PAK1和polo样激酶。然而，CIB1在体内的功能尚不清楚。为了阐明CIB1在全动物中的功能，我们在胚胎干细胞中采用同源重组方法产生了CIB1（-/-）小鼠。尽管Cib1（-/-）小鼠生长正常，但由于精子发生的单倍体期被破坏，雄性小鼠是不育的。这与睾丸大小和精管中生殖细胞数量减少、生殖细胞凋亡增加以及长形精细胞和精子的丧失有关。Cib1（-/-）睾丸也显示细胞周期调节因子Cdc2/Cdk1的mRNA和蛋白表达增加。此外，来自Cib1（-/-）小鼠的小鼠胚胎成纤维细胞（mef）的生长速度比Cib1(+/+) mef慢得多，这表明Cib1调节细胞周期、生精生殖细胞的分化和/或支持Sertoli细胞的分化。
CIB1 is a 22-kDa calcium binding, regulatory protein with similar to 50% homology to calmodulin and calcineurin B. CIB1 is widely expressed and binds to a number of effectors, such as integrin alpha IIb, PAK1, and polo-like kinases, in different tissues. However, the in vivo functions of CIB1 are not well understood. To elucidate the function of CIB1 in whole animals, we used homologous recombination in embryonic stem cells to generate Cib1(-/-) mice. Although Cib1(-/-) mice grow normally, the males are sterile due to disruption of the haploid phase of spermatogenesis. This is associated with reduced testis size and numbers of germ cells in seminiferous tubules, increased germ cell apoptosis, and the loss of elongated spermatids and sperm. Cib1(-/-) testes also show increased mRNA and protein expression of the cell cycle regulator Cdc2/Cdk1. In addition, mouse embryonic fibroblasts (MEFs) derived from Cib1(-/-) mice exhibit a much slower growth rate compared to Cib1(+/+) MEFs, suggesting that CIB1 regulates the cell cycle, differentiation of spermatogenic germ cells, and/or differentiation of supporting Sertoli cells.