Sox9 is sufficient for functional testis development producing fertile male mice in the absence of Sry.
In the dominant mouse mutant Odd Sex, XXOds/+ mice develop as phenotypic, sterile males due to male-pattern expression of Sox9 in XXOds/+ embryonic gonads. To test whether SOX9 was sufficient to generate a fully fertile male in the absence of Sry, we constructed an XY(Sry(-))Ods/+ male mouse, in which the male phenotype is controlled autosomally by the Ods mutation. Mice were initially fertile, but progressively lost fertility until 5-6 months when they were sterile with very few germ cells in the testis. XY(Sry-)Ods/+ males also failed to establish the correct male-specific pattern of vascularization at the time of sex determination, which could be correlated to an inability of XY(Sry-),Ods/+ males to fully down-regulate Wnt4 expression in the embryonic gonad. Increasing the amount of SOX9 by producing homozygous XY(Sry-)Ods/Ods males was able to completely rescue the phenotype and restore correct vascular patterning and long-term fertility. These data indicate that activation of SOX9 in the gonad is sufficient to trigger all the downstream events needed for the development of a fully fertile male and provide evidence that Sox9 may down-regulate Wnt4 expression in the gonad.
Qin
Yangjun
Y
Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX 77030, USA.
Bishop
Colin E
CE
D000818:Animals; D015153:Blotting, Western; D003433:Crosses, Genetic; D015536:Down-Regulation; D017353:Gene Deletion; D018628:Gene Dosage; D018507:Gene Expression Regulation, Developmental; D005799:Genes, Dominant; D024282:Genes, sry; D006609:High Mobility Group Proteins / Q000032:analysis / Q000235:genetics*; D006720:Homozygote; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007248:Infertility, Male / Q000235:genetics*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009929:Organ Size / Q000235:genetics; D010375:Pedigree; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D055758:SOX9 Transcription Factor; D013737:Testis / Q000098:blood supply / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D013997:Time Factors; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics*; D019076:Transgenes; D051153:Wnt Proteins; D060528:Wnt4 Protein
D006609:High Mobility Group Proteins; D011518:Proto-Oncogene Proteins; D055758:SOX9 Transcription Factor; C527933:Sox9 protein, mouse; D014157:Transcription Factors; D051153:Wnt Proteins; D060528:Wnt4 Protein; C555582:Wnt4 protein, mouse