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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Previously uncharacterized roles of platelet-activating factor acetylhydrolase 1b complex in mouse spermatogenesis
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Previously uncharacterized roles of platelet-activating factor acetylhydrolase 1b complex in mouse spermatogenesis

机译:血小板活化因子乙酰水解酶1b复合物在小鼠精子发生中的作用

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Platelet-activating factor (PAF) has been shown to affect sperm motility and acrosomal function, thereby altering fertility. PAF acetylhydrolase 1b (PAFAH1B) hydrolyzes PAF and is composed of three subunits [the lissencephaly (LIS1) protein and alpha1 and alpha2 subunits] and structurally resembles a GTP-hydrolyzing protein. Besides the brain, transcripts for Lis1, alpha1, and alpha2 are localized to meiotic and early haploid germ cells. Here, we report disruptions of the alpha2 (Pafah1b2) and alpha1 (Pafah1b3) genes in mice. Male mice homozygous null for alpha2 (alpha2(-/-)) are infertile, and spermatogenesis is disrupted at mid- or late pachytene stages of meiosis or early spermiogenesis. Whereas mice homozygous mutant for all (alpha1(-/-)) have normal fertility and normal spermatogenesis, those with disruptions of both alpha1 and alpha2 (alpha1(-/-)alpha2(-/-)) manifest an earlier disturbance of spermatogenesis with an onset at preleptotene or leptotene stages of meiosis. Testicular Lis1 protein levels are up-regulated in the alpha2(-/-) and alpha1(-/-)alpha2(-/-) mice. Lowering Lis1 levels by inactivating one allele of Lis1 in a2 null or alpha1/alpha 2 null genetic backgrounds (i.e., alpha2(-/-)Lis1(+/-) or alpha1(-/-)alpha2(-/-)Lis1(+/-)mice) restored spermatogenesis and male fertility. Our data provide evidence for unique roles of the PAFAH1B complex and, particularly, the lissencephaly protein Lis1 in spermatogenesis. [References: 24]
机译:血小板活化因子(PAF)已显示会影响精子运动和顶体功能,从而改变生育能力。 PAF乙酰水解酶1b(PAFAH1B)水解PAF,它由三个亚基[lissencephaly(LIS1)蛋白以及alpha1和alpha2亚基]组成,并且在结构上类似于GTP水解蛋白。除大脑外,Lis1,alpha1和alpha2的转录本定位于减数分裂和早期单倍体生殖细胞。在这里,我们报告在小鼠中的alpha2(Pafah1b2)和alpha1(Pafah1b3)基因的破坏。纯合α2(alpha2(-/-))无效的雄性小鼠不育,并且在减数分裂或早期精子发生的粗线期中期或晚期,精子发生被破坏。所有小鼠的纯合突变体(alpha1(-/-))均具有正常的生育力和正常的精子发生能力,而同时破坏了alpha1和alpha2(alpha1(-/-)alpha2(-/-))的小鼠表现出较早的精子发生障碍在减数分裂的前瘦素或瘦素阶段发作。睾丸Lis1蛋白水平在alpha2(-/-)和alpha1(-/-)alpha2(-/-)小鼠中上调。通过在a2 null或alpha1 / alpha 2 null遗传背景(即alpha2(-/-)Lis1(+/-)或alpha1(-/-)alpha2(-/-)Lis1( +/-)小鼠)恢复了精子发生和雄性育性。我们的数据提供了PAFAH1B复合物,尤其是小脑蛋白Lis1在精子发生中独特作用的证据。 [参考:24]

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