Sox10 gain-of-function causes XX sex reversal in mice: implications for human 22q-linked disorders of sex development

Polanco, J. C., Wilhelm, D, Davidson, T. L., Knight, D and Koopman, P (2010) Sox10 gain-of-function causes XX sex reversal in mice: implications for human 22q-linked disorders of sex development. Human Molecular Genetics, 19 3: 506-516. doi:10.1093/hmg/ddp520


Author Polanco, J. C.
Wilhelm, D
Davidson, T. L.
Knight, D
Koopman, P
Title Sox10 gain-of-function causes XX sex reversal in mice: implications for human 22q-linked disorders of sex development
Journal name Human Molecular Genetics   Check publisher's open access policy
ISSN 0964-6906
Publication date 2010-02-01
Year available 2009
Sub-type Article (original research)
DOI 10.1093/hmg/ddp520
Open Access Status Not yet assessed
Volume 19
Issue 3
Start page 506
End page 516
Total pages 11
Editor Kay Davies
Anthony Wynshaw-Boris
Joel Hirschhorn
Place of publication Oxford , U.K.
Publisher Oxford University Press
Language eng
Subject C1
970106 Expanding Knowledge in the Biological Sciences
060403 Developmental Genetics (incl. Sex Determination)
Abstract Male development in mammals is normally initiated by the Y-linked gene Sry, which activates expression of Sox9, leading to a cascade of gene activity required for testis formation. Although defects in this genetic cascade lead to human disorders of sex development (DSD), only a dozen DSD genes have been identified, and causes of 46,XX DSD (XX maleness) other than SRY translocation are almost completely unknown. Here, we show that transgenic expression of Sox10, a close relative of Sox9, in gonads of XX mice resulted in development of testes and male physiology. The degree of sex reversal correlated with levels of Sox10 expression in different transgenic lines. Sox10 was expressed at low levels in primordial gonads of both sexes during normal mouse development, becoming male-specific during testis differentiation. SOX10 protein was able to activate transcriptional targets of SOX9, explaining at a mechanistic level its ability to direct male development. Because over-expression of SOX10 alone is able to mimic the XX DSD phenotypes associated with duplication of human chromosome 22q13, and given that human SOX10 maps to 22q13.1, our results functionally implicate SOX10 in the etiology of these DSDs.
Keyword SRY-RELATED GENE
CAMPOMELIC DYSPLASIA
TESTIS DIFFERENTIATION
SERTOLI-CELLS
IN-VITRO
CYTOCHROME-P450 ENZYMES
REGULATORY ELEMENTS
PARTIAL DUPLICATION
TRANSGENIC MICE
DEVELOPMENT DSD
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2010 Higher Education Research Data Collection
Institute for Molecular Bioscience - Publications
 
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Created: Sun, 17 Jan 2010, 10:05:51 EST