Abnormal zonae pellucidae in mice lacking ZP1 result in early embryonic loss.

Abnormal zonae pellucidae in mice lacking ZP1 result in early embryonic loss.
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发表时间:
1999-09
期刊:
影响因子:
4.6
通讯作者:
T. Rankin;Prue Talbot;Eric Lee;J. Dean
T. Rankin;Prue Talbot;Eric Lee;J. Dean
中科院分区:
生物学2区
文献类型:
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作者:
T. Rankin;Prue Talbot;Eric Lee;J. Dean

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所有的脊椎动物都有一个包围着排卵卵的蛋壳,它在配子识别中起着关键的作用。这种细胞外基质在真兽目哺乳动物中被称为透明质酸,在小鼠中由三种糖蛋白ZP 1、ZP 2和ZP 3组成。为了研究ZP 1在受精和早期发育中的作用,我们在胚胎干细胞中使用靶向诱变来创建缺乏ZP 1的小鼠品系(Zp 1(tm/tm))。虽然ZP 2和ZP 3组成的透明带周围生长ZP 1(TM/TM)卵母细胞形成的基质比正常卵母细胞周围的带状组织更松散。在一些Zp 1无效卵泡中,这种结构异常导致颗粒细胞异位聚集,位于卵泡基质和卵膜之间,扰乱了正常的卵泡发生。在激素刺激后,从Zp 1无效雌性和正常雌性中排卵的卵数量相当。然而,与雄性交配后,从Zp 1缺失雌性中回收的2细胞胚胎较少,其窝仔明显小于正常小鼠。因此,尽管小鼠ZP 1对精子结合或受精不是必需的,但它对透明卵的结构完整性是必需的,以最大限度地减少早熟孵化和生育力降低。
All vertebrates have an egg shell that surrounds ovulated eggs and plays critical roles in gamete recognition. This extracellular matrix is known as the zona pellucida in eutherian mammals and consists of three glycoproteins, ZP1, ZP2 and ZP3 in the mouse. To investigate the role of ZP1 in fertilization and early development, we have used targeted mutagenesis in embryonic stem cells to create mouse lines (Zp1(tm/tm)) lacking ZP1. Although a zona pellucida composed of ZP2 and ZP3 was formed around growing Zp1(tm/tm) oocytes, the matrix was more loosely organized than zonae around normal oocytes. In some Zp1 null follicles, this structural abnormality resulted in ectopic clusters of granulosa cells, lodged between the zona matrix and the oolemma, that perturbed normal folliculogenesis. Comparable numbers of eggs were ovulated from Zp1 null females and normal females following hormonal stimulation. However, after mating with males, fewer two-cell embryos were recovered from Zp1 null females, and their litters were significantly smaller than those produced by normal mice. Therefore, although mouse ZP1 is not essential for sperm binding or fertilization, it is required for the structural integrity of the zona pellucida to minimize precocious hatching and reduced fecundity.