title: Targeted deletion of the epididymal receptor HE6 results in fluid dysregulation and male infertility.
abstract: 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.
authors.affiliation: Center for Cardiovascular Research-Institute for Pharmacology and Toxicology, Charité-University Medicine, Berlin, Germany. b.davies@murinus.com
authors.forename: Ben
authors.initials: B
authors.lastname: Davies
authors.forename: Claudia
authors.initials: C
authors.lastname: Baumann
authors.forename: Christiane
authors.initials: C
authors.lastname: Kirchhoff
authors.forename: Richard
authors.initials: R
authors.lastname: Ivell
authors.forename: Reinhard
authors.initials: R
authors.lastname: Nubbemeyer
authors.forename: Ursula-Friederike
authors.initials: UF
authors.lastname: Habenicht
authors.forename: Franz
authors.initials: F
authors.lastname: Theuring
authors.forename: Ulrich
authors.initials: U
authors.lastname: Gottwald
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D004822:Epididymis / Q000378:metabolism / Q000473:pathology*; D017353:Gene Deletion; D007248:Infertility, Male / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000378:metabolism; D013737:Testis / Q000473:pathology
chemical_list: C105986:ADGRG2 protein, human; C492742:Adgrg2 protein, mouse; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled