• PMID: 17591950
• Gene Name: GJA1
• Condition: Required for normal testicular development and spermatogenesis
• Association: Associated
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Required for normal testicular development and spermatogenesis

A sertoli cell-specific knockout of connexin43 prevents initiation of spermatogenesis

Brehm R, Zeiler M, Rüttinger C, Herde K, Kibschull M, Winterhager E, Willecke K, Guillou F, Lécureuil C, Steger K, Konrad L, Biermann K, Failing K, Bergmann M.

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. FAU - Brehm, Ralph AU - Brehm R AD - Justus-Liebig-Universitaet, Institut fuer Veterinaer-Anatomie, -Histologie, und -Embryologie, Frankfurter Strasse 98, Giessen, Germany. ralph.h.brehm@vetmed.uni-giessen.de FAU - Zeiler, Martina AU - Zeiler M FAU - Rüttinger, Christina AU - Rüttinger C FAU - Herde, Katja AU - Herde K FAU - Kibschull, Mark AU - Kibschull M FAU - Winterhager, Elke AU - Winterhager E FAU - Willecke, Klaus AU - Willecke K FAU - Guillou, Florian AU - Guillou F FAU - Lécureuil, Charlotte AU - Lécureuil C FAU - Steger, Klaus AU - Steger K FAU - Konrad, Lutz AU - Konrad L FAU - Biermann, Katharina AU - Biermann K FAU - Failing, Klaus AU - Failing K