Journal article
Identification of SOX3 as an XX male sex reversal gene in mice and humans
E Sutton, J Hughes, S White, R Sekido, J Tan, V Arboleda, N Rogers, K Knower, L Rowley, H Eyre, K Rizzoti, D McAninch, J Goncalves, J Slee, E Turbitt, D Bruno, H Bengtsson, V Harley, E Vilain, A Sinclair Show all
Journal of Clinical Investigation | Published : 2011
DOI: 10.1172/JCI42580
Abstract
Sex 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 mi..
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Awarded by Eunice Kennedy Shriver National Institute of Child Health and Human Development
Funding Acknowledgements
The authors thank Peter Koopman and Josephine Bowles for sharing unpublished data and useful discussions, Terry Speed for assistance with microarray analysis, and Frank Grutzner for critical reading of the manuscript We also thank Sandra Piltz, Mizuho Mamiya, Rhonda Hutchinson, Julie Scott, and the staff of the University of Adelaide Laboratory Animal Services for technical assistance The authors also thank Tiago Rocha for patient A's clinical evaluation and the staff of Unidade de Citogenerica of Instituto Nacional de Saude Ricardo Jorge for the chromosome analysis, as well as the contribution of the patients Involved in the study We gratefully acknowledge funding support from the Australian Research Council (P Thomas), the Australian National Health and Medical Research Council (P Thomas, S White, A Sinclair, and V Harley), the UK Medical Research Council (U117512772) (R Lovell Badge), the Helen Macpherson Smith Trust (A Sinclair), the Fundacao para a Ciencia e a Tecnologia (FCT, POCTI/SAU/97/2001) and the Centro de Investigacao em Genetica Molecular Humana da Universidade Nova de Lisboa (J Goncalves), the Doris Duke Charitable Foundation (E Vilain), and the Louis Jeantet Foundation (R. Lovell Badge) Paul Thomas is a Pfizer Australia Research Fellow