Human Molecular Genetics Advance Access published online on March 24, 2005
Human Molecular Genetics, doi:10.1093/hmg/ddi133
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1 Department of Obstetrics & Gynecology, Baylor College of Medicine, Houston TX 77030
* To whom correspondence should be addressed. 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. In order 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 at 5-6 months 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.
Received January 6, 2005
Revised March 7, 2005
Accepted March 13, 2005
Article
Sox9 is sufficient for functional testis development producing fertile male mice in the absence of Sry
2 Department of Obstetrics & Gynecology, Baylor College of Medicine, 6550 Fannin Street (880), Houston, TX 77030; Department of Molecular & Human Genetics, Baylor College of Medicine, Houston TX 77030
Colin E. Bishop, E-mail: bishop{at}bcm.tmc.edu
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