Davies Ben, Baumann Claudia, Kirchhoff Christiane, Ivell Richard, Nubbemeyer Reinhard, Habenicht Ursula-Friederike, Theuring Franz, Gottwald Ulrich
Center for Cardiovascular Research-Institute for Pharmacology and Toxicology, Charité-University Medicine, Berlin, Germany.
Mol Cell Biol. 2004 Oct;24(19):8642-8. doi: 10.1128/MCB.24.19.8642-8648.2004.
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.
人附睾蛋白6（HE6；也称为GPR64）是G蛋白偶联受体LNB-7TM（B(2)）亚家族的一个孤儿成员。该家族成员的特征是同时存在一个促胰液素样（II型）七跨膜（7TM）结构域和一个长的细胞粘附样细胞外结构域。HE6在输出小管和附睾起始段中特异性表达，这些管道系统参与精子成熟过程。在此，我们报道靶向敲除小鼠HE6基因的7TM结构域会导致雄性不育。突变小鼠显示出输出小管内液体重吸收失调，导致睾丸内液体蓄积以及随后输出小管内精子停滞。HE6基因敲除小鼠的生育表型将该受体确定为未来男性避孕药的潜在非甾体、非睾丸靶点，并确定了这个不寻常基因家族成员的体内功能。
