Human Molecular Genetics Advance Access originally published online on March 24, 2005
Human Molecular Genetics 2005 14(9):1221-1229; doi:10.1093/hmg/ddi133
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Published by Oxford University Press 2005.
Sox9 is sufficient for functional testis development producing fertile male mice in the absence of Sry
1Department of Obstetrics and Gynecology and 2Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA
* To whom correspondence should be addressed at: Department of Obstetrics and Gynecology, Baylor College of Medicine, 6550 Fannin Street (880), Houston, TX 77030, USA. Tel: +1 7137988221; Fax: +1 7137985074; Email: bishop{at}bcm.tmc.edu
Received January 6, 2005; Accepted March 13, 2005
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.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  D. M. Maatouk, L. DiNapoli, A. Alvers, K. L. Parker, M. M. Taketo, and B. Capel Stabilization of {beta}-catenin in XY gonads causes male-to-female sex-reversal Hum. Mol. Genet., October 1, 2008; 17(19): 2949 - 2955. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. T. Maciel-Guerra, M. P. de Mello, F. B. Coeli, M. L. Ribeiro, M. L. Miranda, A. P. Marques-de-Faria, M. T. M. Baptista, S. G. Moraes, and G. Guerra-Junior XX Maleness and XX True Hermaphroditism in SRY-Negative Monozygotic Twins: Additional Evidence for a Common Origin J. Clin. Endocrinol. Metab., February 1, 2008; 93(2): 339 - 343. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. DiNapoli and B. Capel SRY and the Standoff in Sex Determination Mol. Endocrinol., January 1, 2008; 22(1): 1 - 9. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. J. O'Shaughnessy, P. J. Baker, A. Monteiro, S. Cassie, S. Bhattacharya, and P. A. Fowler Developmental Changes in Human Fetal Testicular Cell Numbers and Messenger Ribonucleic Acid Levels during the Second Trimester J. Clin. Endocrinol. Metab., December 1, 2007; 92(12): 4792 - 4801. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Feng, N. V Bogatcheva, A. Truong, B. Korchin, C. E Bishop, T. Klonisch, I. U Agoulnik, and A. I Agoulnik Developmental Expression and Gene Regulation of Insulin-like 3 Receptor RXFP2 in Mouse Male Reproductive Organs Biol Reprod, October 1, 2007; 77(4): 671 - 680. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. J. Bouma, L. L. Washburn, K. H. Albrecht, and E. M. Eicher Correct dosage of Fog2 and Gata4 transcription factors is critical for fetal testis development in mice PNAS, September 18, 2007; 104(38): 14994 - 14999. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S Pujar, K. Kothapalli, H. Goring, and V. Meyers-Wallen Linkage to CFA29 Detected in a Genome-Wide Linkage Screen of a Canine Pedigree Segregating Sry-Negative XX Sex Reversal J. Hered., August 3, 2007; (2007) esm028v2. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Wilhelm, S. Palmer, and P. Koopman Sex Determination and Gonadal Development in Mammals Physiol Rev, January 1, 2007; 87(1): 1 - 28. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Rajender, K. Thangaraj, N. J. Gupta, N. Leelavathy, D. S. Rani, R. G. Nambiar, V. Kalavathy, S. T. Santhiya, S. Rajangam, P. M. Gopinath, et al. A Novel Human Sex-Determining Gene Linked to Xp11.21-11.23 J. Clin. Endocrinol. Metab., October 1, 2006; 91(10): 4028 - 4036. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Barrionuevo, S. Bagheri-Fam, J. Klattig, R. Kist, M. M. Taketo, C. Englert, and G. Scherer Homozygous Inactivation of Sox9 Causes Complete XY Sex Reversal in Mice Biol Reprod, January 1, 2006; 74(1): 195 - 201. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Nowacka, W. Nizanski, M. Klimowicz, S. Dzimira, and M. Switonski Lack of the SOX9 Gene Polymorphism in Sex Reversal Dogs (78,XX; SRY negative) J. Hered., November 1, 2005; 96(7): 797 - 802. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Kanai, R. Hiramatsu, S. Matoba, and T. Kidokoro From SRY to SOX9: Mammalian Testis Differentiation J. Biochem., July 1, 2005; 138(1): 13 - 19. [Abstract] [Full Text] [PDF]
|
|