title: Long-range activation of Sox9 in Odd Sex (Ods) mice.
abstract: The Odd Sex mouse mutation arose in a transgenic line of mice carrying a tyrosinase minigene driven by the dopachrome tautomerase (Dct) promoter 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 promoter is capable of acting over a distance of 1 Mb to induce inappropriate expression of Sox9 in the retinal pigmented epithelium 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 promoter element interacting with gonad-specific enhancer elements to produce the observed male pattern expression of Sox9 in the embryonic gonads.
authors.affiliation: Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Yangjun
authors.initials: Y
authors.lastname: Qin
authors.forename: Ling-kun
authors.initials: LK
authors.lastname: Kong
authors.forename: Christophe
authors.initials: C
authors.lastname: Poirier
authors.forename: Cavatina
authors.initials: C
authors.lastname: Truong
authors.forename: Paul A
authors.initials: PA
authors.lastname: Overbeek
authors.forename: Colin E
authors.initials: CE
authors.lastname: Bishop
mesh_terms: D000818:Animals; D012734:Disorders of Sex Development; D004742:Enhancer Elements, Genetic / Q000235:genetics; D005123:Eye / Q000378:metabolism / Q000473:pathology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006066:Gonads / Q000378:metabolism; D006609:High Mobility Group Proteins / Q000235:genetics / Q000378:metabolism*; D019746:Intramolecular Oxidoreductases / Q000235:genetics; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics*; D010858:Pigmentation / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D055758:SOX9 Transcription Factor; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D019076:Transgenes / Q000235:genetics
chemical_list: D006609:High Mobility Group Proteins; D055758:SOX9 Transcription Factor; C527933:Sox9 protein, mouse; D014157:Transcription Factors; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase