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Identification of SOX3 as an XX male sex reversal gene in mice and humans

2011-01Journal article Open access
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dc.contributor.authorSutton, Edwina
dc.contributor.authorHughes, James
dc.contributor.authorWhite, Stefan
dc.contributor.authorSekido, Ryohei
dc.contributor.authorTan, Jacqueline
dc.contributor.authorArboleda, Valerie
dc.contributor.authorRogers, Nicholas
dc.contributor.authorKnower, Kevin
dc.contributor.authorRowley, Lynn
dc.contributor.authorEyre, Helen
dc.contributor.authorRizzoti, Karine
dc.contributor.authorMcAninch, Dale
dc.contributor.authorGonçalves, João
dc.contributor.authorSlee, Jennie
dc.contributor.authorTurbitt, Erin
dc.contributor.authorBruno, Damien
dc.contributor.authorBengtsson, Henrik
dc.contributor.authorHarley, Vincent
dc.contributor.authorVilain, Eric
dc.contributor.authorSinclair, Andrew
dc.contributor.authorLovell-Badge, Robin
dc.contributor.authorThomas, Paul
dc.date.accessioned2012-03-15T17:30:49Z
dc.date.available2012-03-15T17:30:49Z
dc.date.issued2011-01
dc.description.abstractSex in mammals is genetically determined and is defined at the cellular level by sex chromosome complement (XY males and XX females). The Y chromosome-linked gene sex-determining region Y (SRY) is believed to be the master initiator of male sex determination in almost all eutherian and metatherian mammals, functioning to upregulate expression of its direct target gene Sry-related HMG box-containing gene 9 (SOX9). Data suggest that SRY evolved from SOX3, although there is no direct functional evidence to support this hypothesis. Indeed, loss-of-function mutations in SOX3 do not affect sex determination in mice or humans. To further investigate Sox3 function in vivo, we generated transgenic mice overexpressing Sox3. Here, we report that in one of these transgenic lines, Sox3 was ectopically expressed in the bipotential gonad and that this led to frequent complete XX male sex reversal. Further analysis indicated that Sox3 induced testis differentiation in this particular line of mice by upregulating expression of Sox9 via a similar mechanism to Sry. Importantly, we also identified genomic rearrangements within the SOX3 regulatory region in three patients with XX male sex reversal. Together, these data suggest that SOX3 and SRY are functionally interchangeable in sex determination and support the notion that SRY evolved from SOX3 via a regulatory mutation that led to its de novo expression in the early gonad.por
dc.identifier.citationJ Clin Invest. 2011 Jan;121(1):328-41. Epub 2010 Dec 22por
dc.identifier.issn0021-9738
dc.identifier.otherdoi:10.1172/JCI42580
dc.identifier.urihttp://hdl.handle.net/10400.18/812
dc.language.isoengpor
dc.peerreviewedyespor
dc.publisherAmerican Society for Clinical Investigationpor
dc.relation.publisherversionhttp://www.jci.org/articles/view/42580por
dc.subjectDoença Genéticaspor
dc.subjectSOX3por
dc.subjectXX Malepor
dc.subjectHomem XXpor
dc.subjectSex Reversalpor
dc.subjectReversão Sexualpor
dc.subjectDeterminação do Sexopor
dc.subjectSex Determinationpor
dc.subjectSRYpor
dc.subjectSOX9por
dc.titleIdentification of SOX3 as an XX male sex reversal gene in mice and humanspor
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage341por
oaire.citation.startPage328por
oaire.citation.titleJournal of Clinical Investigationpor
rcaap.rightsopenAccesspor
rcaap.typearticlepor

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