ZONA PELLUCIDA BINDING PROTEINS IN SPERM-EGG INTERACTIONS

项目#3：精卵相互作用中的透明带结合蛋白 生殖是一个复杂的多因素过程，数百个哺乳动物基因已经被 被鉴定为在生殖中起作用。精子与卵丘的结合， 透明膜，最终卵质膜是未来配子融合的必要步骤 基因组和受精卵组织的起始。正如所料，精子和卵子的蛋白质 在精子和卵子的最初和随后的相互作用中发挥积极作用。许多起作用的蛋白 从精子与透明质膜结合到精子DNA进入卵子的关键或支持作用 细胞质基本上是未知的。我们的假设是，这两个透明质酸结合蛋白是 哺乳动物精子蛋白在受精的一个或多个步骤中起关键作用。具体目标是：1） 研究ZPBP1：ZPBP2结合和精子-卵子体外相互作用; 2）产生和分析缺乏ZPBP2的小鼠 ZPBP1、ZPBP2或两者;以及3）确定精子与卵子结合缺陷的男性是否具有 ZPBP1或ZPBP2基因或其他候选基因中的突变。这些研究将对 了解体内精子与卵子相互作用的关键蛋白质和机制，将有助于 定义与人类男性不育有关的必需蛋白质。

Project #3: Zona Pellucida Binding Proteins In Sperm Egg Interactions Reproduction is a complex and multifactorial process, and hundreds of mammalian genes have already been identified to function in reproduction. The binding of spermatozoa to the cumulus oophorus, the egg zona pellucida, and eventually the egg plasma membrane are essential steps for the future fusion of gamete genomes and the initiation of the zygote organization. As might be expected, both sperm and egg proteins play active roles in the initial and subsequent interactions of sperm and eggs. Many of the proteins that play key or supporting roles from binding of sperm to the zona pellucida until entry of the sperm DNA into the egg cytoplasm are largely unknown. Our overlying hypothesis is that the two zona pellucida binding proteins are critical mammalian sperm proteins in one or more of these steps in fertilization. The Specific Aims are: 1) Study ZPBP1:ZPBP2 binding and sperm-egg interactions in vitro; 2) Generate and analyze mice lacking ZPBP1, ZPBP2, or both; and 3) Determine whether men with defective binding of their sperm to eggs have mutations in ZPBP1 or ZPBP2 genes or additional candidate genes. These studies will be important for understanding the key proteins and mechanisms involved in sperm:egg interactions in vivo and will help to define essential proteins implicated in human male infertility.