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468387.0 [No comment] 18.03.2010 11:48 Released

ID: 468387.0, MPI für molekulare Genetik / Department of Human Molecular Genetics
Testis cord differentiation after the sex determination stage is independent of Sox9 but fails in the combined absence of Sox9 and Sox8
Authors:Barrionuevo, Francisco; Georg, Ina; Scherthan, Harry; Lécureuil, Charlotte; Guillou, Florian; Wegner, Michael; Scherer, Gerd
Date of Publication (YYYY-MM-DD):2009-03-15
Title of Journal:Developmental Biology
Issue / Number:2
Start Page:301
End Page:312
Copyright:© 2009 Elsevier B.V.
Review Status:not specified
Audience:Experts Only
Abstract / Description:Sox9 and Sox8 are transcription factors expressed in embryonic and postnatal Sertoli cells of the mouse testis. Sox9 inactivation prior to the sex determination stage leads to complete XY sex reversal. In contrast, there is normal embryonic testis development in Sox8 mutants which are initially fertile, but later develop progressive seminiferous tubule failure and infertility. To determine whether Sox9 is required for testis development after the initial steps of sex determination, we crossed Sox9flox mice with an AMH-Cre transgenic line thereby completely deleting Sox9 in Sertoli cells by E14.0. Conditional Sox9 null mutants show normal embryonic testis development and are initially fertile, but, like Sox8−/− mutants, become sterile from dysfunctional spermatogenesis at about 5 months. To see whether Sox8 may compensate for the absence of Sox9 during embryonic testis differentiation, we generated a Sox9 conditional knockout on a Sox8 mutant background. In the double mutants, differentiation of testis cords into seminiferous testis tubules ceases after P6 in the absence of one Sox8 allele, and after P0 in the absence of both Sox8 alleles, leading to complete primary infertility. Sox9,Sox8 double nullizygous testes show upregulation of early ovary-specific markers and downregulation of Sertoli intercellular junctions at E15.5. Their very low Amh levels still cause complete regression of the Müllerian duct but with reduced penetrance. This study shows that testis cord differentiation is independent of Sox9, and that concerted Sox9 and Sox8 function in post E14.0 Sertoli cells is essential for the maintenance of testicular function.
Free Keywords:Sox9; Sox8; Testis cords; Amh; Mouse testis differentiation
Comment of the Author/Creator:email: gerd.scherer@uniklinik-freiburg.de
External Publication Status:published
Document Type:Article
Communicated by:Hans-Hilger Ropers
Affiliations:MPI für molekulare Genetik
External Affiliations:Institute of Human Genetics and Anthropology, University of Freiburg, Breisacherstr. 33, D-79106 Freiburg, Germany
Faculty for Biology, University of Freiburg, Schänzlestr. 1, D-79104 Freiburg, Germany
Institut für Radiobiologie der Bundeswehr, D-90837 München, Germany
Unité Mixte de Recherche 6175, Physiologie de la Reproduction, Institut National de la Recherche Agronomique, Centre National de la Recherche Scientifique, Université de Tours, Haras Nationaux, F-37380 Nouzilly, France
Institut für Biochemie, Emil-Fischer-Zentrum, Universität Erlangen, D-91054 Erlangen, Germany