Targeted inactivation of the mouse epididymal beta-defensin 41 alters sperm flagellar beat pattern and zona pellucida binding
Targeted inactivation of the mouse epididymal beta-defensin 41 alters sperm flagellar beat pattern and zona pellucida binding
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DOI：
10.1016/j.mce.2016.03.013
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发表时间：
2016-05-15
影响因子：
4.1
通讯作者：
Sipila, Petra
中科院分区：
文献类型：
--
作者：
Bjorkgren, Ida;Alvarez, Luis;Sipila, Petra
在附睾成熟过程中，精子通过与附睾上皮分泌的蛋白质相互作用而获得逐渐游动的能力。附睾中表达的β-防御素蛋白在女性生殖道获能和过度激活期间继续调节精子活力。我们通过将 iCre 重组酶插入到该基因的第一个外显子中，生成小鼠模型，从而表征了小鼠 β-防御素 41 (DEFB41)。纯合 Defb41(iCre/iCre) 敲入小鼠缺乏 Defb41 表达，并在近端附睾主细胞中表现出 iCre 重组酶活性。杂合 Defb41(iCre/+) 小鼠可用于生成附睾特异性条件敲除小鼠模型。纯合 Defb41(iCre/iCre) 精子表现出精子运动缺陷，鞭毛主要在前钩构象中弯曲，而获能的野生型精子更经常表现出反钩构象。这导致 Defb41(iCre/liCre) 精子的直线运动能力降低，与卵母细胞的结合能力减弱。因此，DEFB41 是精子正常成熟所必需的。 (C) 2016 Elsevier Ireland Ltd. 保留所有权利。
During epididymal maturation, sperm acquire the ability to swim progressively by interacting with proteins secreted by the epididymal epithelium. Beta-defensin proteins, expressed in the epididymis, continue to regulate sperm motility during capacitation and hyperactivation in the female reproductive tract. We characterized the mouse beta-defensin 41 (DEFB41), by generating a mouse model with iCre recombinase inserted into the first exon of the gene. The homozygous Defb41(iCre/iCre) knock-in mice lacked Defb41 expression and displayed iCre recombinase activity in the principal cells of the proximal epididymis. Heterozygous Defb41(iCre/+) mice can be used to generate epididymis specific conditional knock-out mouse models. Homozygous Defb41(iCre/iCre) sperm displayed a defect in sperm motility with the flagella primarily bending in the pro-hook conformation while capacitated wild-type sperm more often displayed the anti-hook conformation. This led to a reduced straight line motility of Defb41(iCre/liCre) sperm and weaker binding to the oocyte. Thus, DEFB41 is required for proper sperm maturation. (C) 2016 Elsevier Ireland Ltd. All rights reserved.