Fertility and taxon-specific sperm binding persist after replacement of mouse sperm receptors with human homologs

Fertility and taxon-specific sperm binding persist after replacement of mouse sperm receptors with human homologs
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DOI:
10.1016/s1534-5807(03)00195-3
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发表时间:
2003-07-01
期刊:
影响因子:
11.8
通讯作者:
Dean, J
Dean, J
中科院分区:
生物学1区
文献类型:
--
作者:
Rankin, TL;Coleman, JS;Dean, J

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排卵小鼠卵周围的透明膜含有三种糖蛋白,其中两种(ZP 2和ZP 3)是已报道的精子受体。受精后,透明卵通过ZP 2的分裂而被修饰,精子不再结合。交叉精子结合在哺乳动物中是有限的,人类精子不与小鼠卵子结合。使用转基因用人同源物替换小鼠ZP 2和/或ZP 3,已经建立了具有人-小鼠嵌合透明带的小鼠系。出乎意料的是,小鼠(而不是人类)的精子与huZP 2结合,huZP 2/huZP 3拯救了卵子,与小鼠精子体外受精的卵子发育成两细胞胚胎,并且拯救的小鼠具有生育能力。同样出乎意料的是,人类ZP 2在受精后仍然未被切割,小鼠精子继续结合早期拯救胚胎。这些观察结果是一致的模型,其中精子结合所需的透明质酸的超分子结构是由ZP 2的分裂状态调制。
The zona pellucida surrounding ovulated mouse eggs contains three glycoproteins, two of which (ZP2 and ZP3) are reported sperm receptors. After fertilization, the zona pellucida is modified ad minimus by cleavage of ZP2, and sperm no longer bind. Crosstaxa sperm binding is limited among mammals, and human sperm do not bind to mouse eggs. Using transgenesis to replace mouse ZP2 and/or ZP3 with human homologs, mouse lines with human-mouse chimeric zonae pellucidae have been established. Unexpectedly, mouse, but not human, sperm bind to huZP2 and huZP2/huZP3 rescue eggs, eggs fertilized in vitro with mouse sperm progress to two-cell embryos, and rescue mice are fertile. Also unanticipated, human ZP2 remains uncleaved after fertilization, and mouse sperm continue to bind early rescue embryos. These observations are consistent with a model in which the supramolecular structure of the zona pellucida necessary for sperm binding is modulated by the cleavage status of ZP2.