title: A sertoli cell-specific knockout of connexin43 prevents initiation of spermatogenesis.
abstract: The predominant testicular gap junctional protein connexin43 (cx43) is located between neighboring Sertoli cells (SCs) and between SCs and germ cells. It is assumed to be involved in testicular development, cell differentiation, initiation, and maintenance of spermatogenesis with alterations of its expression being correlated with various testicular disorders. Because total disruption of the cx43 gene leads to perinatal death, we generated a conditional cx43 knockout (KO) mouse using the Cre/loxP recombination system, which lacks the cx43 gene solely in SCs (SCCx43KO), to evaluate the SC-specific functions of cx43 on spermatogenesis in vivo. Adult SCCx43KO(-/-) mice showed normal testis descent and development of the urogenital tract, but testis size and weight were drastically lower compared with heterozygous and wild-type littermates. Histological analysis and quantitation of mRNA expression of germ cell-specific marker genes revealed a significant reduction in the number of spermatogonia but increased SC numbers/tubule with only a few tubules left showing normal spermatogenesis. Thus, SC-specific deletion of cx43 mostly resulted in an arrest of spermatogenesis at the level of spermatogonia or SC-only syndrome and in intratubular SC clusters. Our data demonstrate for the first time that cx43 expression in SCs is an absolute requirement for normal testicular development and spermatogenesis.
authors.affiliation: Justus-Liebig-Universitaet, Institut fuer Veterinaer-Anatomie, -Histologie, und -Embryologie, Frankfurter Strasse 98, Giessen, Germany. ralph.h.brehm@vetmed.uni-giessen.de
authors.forename: Ralph
authors.initials: R
authors.lastname: Brehm
authors.forename: Martina
authors.initials: M
authors.lastname: Zeiler
authors.forename: Christina
authors.initials: C
authors.lastname: Rüttinger
authors.forename: Katja
authors.initials: K
authors.lastname: Herde
authors.forename: Mark
authors.initials: M
authors.lastname: Kibschull
authors.forename: Elke
authors.initials: E
authors.lastname: Winterhager
authors.forename: Klaus
authors.initials: K
authors.lastname: Willecke
authors.forename: Florian
authors.initials: F
authors.lastname: Guillou
authors.forename: Charlotte
authors.initials: C
authors.lastname: Lécureuil
authors.forename: Klaus
authors.initials: K
authors.lastname: Steger
authors.forename: Lutz
authors.initials: L
authors.lastname: Konrad
authors.forename: Katharina
authors.initials: K
authors.lastname: Biermann
authors.forename: Klaus
authors.initials: K
authors.lastname: Failing
authors.forename: Martin
authors.initials: M
authors.lastname: Bergmann
mesh_terms: D000818:Animals; D018031:Connexin 43 / Q000235:genetics / Q000502:physiology*; D004822:Epididymis / Q000033:anatomy & histology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D012708:Sertoli Cells / Q000378:metabolism*; D013091:Spermatogenesis / Q000235:genetics*; D013093:Spermatogonia; D013737:Testis / Q000166:cytology / Q000254:growth & development*
chemical_list: D018031:Connexin 43