Formin-2, polyploidy, hypofertility and positioning of the meiotic spindle in mouse oocytes
Formin-2, polyploidy, hypofertility and positioning of the meiotic spindle in mouse oocytes
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DOI：
10.1038/ncb880
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发表时间：
2002-12-01
影响因子：
21.3
通讯作者：
Leder, P
中科院分区：
文献类型：
--
作者：
Leader, B;Lim, H;Leder, P
哺乳动物的成功繁殖需要一个有能力的卵子，它是在减数分裂过程中通过两次不对称细胞分裂形成的。在此，我们表明一个最近鉴定出的成蛋白同源（FH）基因，成蛋白 - 2（Fmn2），是一个母源效应基因，在卵母细胞中表达，并且是减数第一次分裂中期进程所必需的。Fmn2缺失（-/-）的卵母细胞在减数第一次分裂期间无法正确定位中期纺锤体，也无法形成第一极体。我们证明在减数第一次分裂中期，Fmn2是微管非依赖性染色质定位所必需的。Fmn2缺失（-/-）的卵母细胞受精会导致多倍体胚胎形成、Fmn2缺失（-/-）的雌性反复流产以及生育力低下。将Fmn2 mRNA注射到Fmn2缺陷的卵母细胞中可挽救减数第一次分裂中期的阻滞。鉴于减数分裂成熟过程中的错误会导致严重的出生缺陷，并且是人类染色体非整倍性和流产的最常见原因，对Fmn2的研究可能会更好地理解不育和出生缺陷。
Successful reproduction in mammals requires a competent egg, which is formed during meiosis through two assymetrical cell divisions. Here, we show that a recently identified formin homology (FH) gene, formin-2 (Fmn2), is a maternal-effect gene that is expressed in oocytes and is required for progression through metaphase of meiosis I. Fmn2(-/-) oocytes cannot correctly position the metaphase spindle during meiosis I and form the first polar body. We demonstrate that Fmn2 is required for microtubule-independent chromatin positioning during metaphase I. Fertilization of Fmn2(-/-) oocytes results in polyploid embryo formation, recurrent pregnancy loss and sub-fertility in Fmn2(-/-) females. Injection of Fmn2 mRNA into Fmn2-deficient oocytes rescues the metaphase I block. Given that errors in meiotic maturation result in severe birth defects and are the most common cause of chromosomal aneuploidy and pregnancy loss in humans, studies of Fmn2 may provide a better understanding of infertility and birth defects.