Human Molecular Genetics Advance Access published online on April 28, 2004
Human Molecular Genetics, doi:10.1093/hmg/ddh141
© 2004 by Oxford University Press
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1 Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston TX 77030
* To whom correspondence should be addressed. E-mail: bishop{at}bcm.tmc.edu.
The Odd Sex mouse mutation arose in a transgenic line of mice carring a tyrosinase minigene driven by the dopachrome tautomerase (Dct) promotor region. The minigene integrated 0.98 Mb upstream of Sox9 and was accompanied by a deletion of 134 Kb. This mutation causes female to male sex reversal in XX Ods/+ mice, and a characteristic eye phenotype of microphthalmia with cataracts in all mice carrying the transgene. Ods causes sex reversal in the absence of Sry by upregulating Sox9 expression and maintaining a male pattern of Sox9 expression in XX Ods/+ embryonic gonads. This expression, which begins at E11.5, triggers downstream events leading to the formation of a testis. We report here that the 134 kb deletion, in itself, is insufficient to cause sex reversal. We demonstrate that in Ods, the Dct promotor is capable of acting over a distance of 1Mb to induce inappropriate expression of Sox9 in the retinal pigmented epithelium (RPE) of the eye, causing the observed microphthalmia. In addition, it induces Sox9 expression in the melanocytes where it causes pigmentation defects. We propose that Ods sex reversal is due to the Dct promotor element interacting with gonad-specific enhancer elements to produce the observed male pattern expression of Sox9 in the embryonic gonads.
Article
Long-range activation of Sox9 in Odd Sex (Ods) mice
2 Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston TX 77030
3 Department of Obstetrics and Gynecology, Baylor College of Medicine, 6550 Fannin Street, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston TX 77030
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