Reduced fertility in male mice deficient in the zinc metallopeptidase NL1
Reduced fertility in male mice deficient in the zinc metallopeptidase NL1
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DOI：
10.1128/mcb.24.10.4428-4437.2004
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发表时间：
2004-05-01
影响因子：
5.3
通讯作者：
Charron, J
中科院分区：
文献类型：
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作者：
Carpentier, M;Guillemette, C;Charron, J
锌金属内肽酶M13家族成员在多种神经肽和多肽激素的代谢中发挥重要作用，已被确定为重要的治疗靶点。最近，小鼠NL1蛋白被发现，它是该家族的一个新成员，主要以分泌型蛋白的形式在睾丸中表达。为了确定其生理作用(S)，我们使用了一种基因打靶策略，通过同源重组来破坏内源性小鼠的NL1基因，并产生NL1突变小鼠。NL1(-/-)小鼠存活并发育正常。提示NL1的合子表达不是发育所必需的。然而，NL1(-/-)雄性比它们的野生型兄弟姐妹产下的孩子更小，这表明特定的雄性生育问题。生育力下降可能是由两个受损的过程造成的，即卵子受精减少和受精卵早期发育受扰。这两种表型不是由于睾丸的大体解剖改变或精子发生受损造成的。基本的精子参数也是正常的。因此，我们的发现表明，NL1在小鼠体内的作用之一与精子功能有关，并且调节受精和体内早期胚胎发育的过程。
Members of the M13 family of zinc metalloendopeptidases have been shown to play critical roles in the metabolism of various neuropeptides and peptide hormones, and they have been identified as important therapeutic targets. Recently, a mouse NL1 protein, a novel member of the family, was identified and shown to be expressed mainly in the testis as a secreted protein. To define its physiological role(s), we used a gene targeting strategy to disrupt the endogenous murine Nl1 gene by homologous recombination and generate Nl1 mutant mice. The Nl1(-/-) mice were viable and developed normally,. suggesting that zygotic expression of Nl1 is not required for development. However, Nl1(-/-) males produced smaller litters than their wild-type siblings, indicating specific male fertility problems. Reduced fertility may be explained by two impaired processes, decreased egg fertilization and perturbed early development of fertilized eggs. These two phenotypes did not result from gross anatomical modifications of the testis or from impaired spermatogenesis. Basic sperm parameters were also normal. Thus, our findings suggest that one of the roles of NL1 in mice is related to sperm function and that NL1 modulates the processes of fertilization and early embryonic development in vivo.