Targeted deletion of the epididymal receptor HE6 results in fluid dysregulation and male infertility
Targeted deletion of the epididymal receptor HE6 results in fluid dysregulation and male infertility
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DOI：
10.1128/mcb.24.19.8642-8648.2004
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发表时间：
2004-10-01
影响因子：
5.3
通讯作者：
Gottwald, U
中科院分区：
文献类型：
--
作者：
Davies, B;Baumann, C;Gottwald, U
人附睾蛋白 6（HE6；也称为 GPR64）是 G 蛋白偶联受体 LNB-7TM (B-2) 亚家族的孤儿成员。家族成员的特征是双重存在促胰液素样（II 型）七跨膜 (7TM) 结构域和长细胞粘附样细胞外结构域。 HE6 在传出小管和附睾起始段（参与精子成熟的导管系统）内特异性表达。在此，我们报告了小鼠 HE6 基因 7TM 结构域的靶向删除会导致男性不育。突变小鼠表现出传出小管内液体重吸收的失调，导致睾丸中液体积聚，随后精子在传出管内停滞。 HE6 敲除小鼠的生育表型表明该受体是未来男性避孕药的潜在非类固醇、非睾丸靶标，并确定了该不寻常基因家族成员的体内功能。
Human epididymal protein 6 (HE6; also known as GPR64) is an orphan member of the LNB-7TM (B-2) subfamily of G-protein-coupled receptors. Family members are characterized by the dual presence of a secretin-like (type II) seven-transmembrane (7TM) domain and a long cell adhesion-like extracellular domain. HE6 is specifically expressed within the efferent ductules and the initial segment of the epididymis, ductal systems involved in spermatozoon maturation. Here, we report that targeted deletion of the 7TM domain of the murine HE6 gene results in male infertility. Mutant mice reveal a dysregulation of fluid reabsorbtion within the efferent ductules, leading to a backup of fluid accumulation in the testis and a subsequent stasis of spermatozoa within the efferent ducts. The fertility phenotype of HE6 knockout mice identifies this receptor as a potential nonsteroidal, nontesticular target for future male contraceptives and identifies an in vivo function for a member of this unusual gene family.