title: Mammalian sex determination—insights from humans and mice.
abstract: Disorders of sex development (DSD) are congenital conditions in which the development of chromosomal, gonadal, or anatomical sex is atypical. Many of the genes required for gonad development have been identified by analysis of DSD patients. However, the use of knockout and transgenic mouse strains have contributed enormously to the study of gonad gene function and interactions within the development network. Although the genetic basis of mammalian sex determination and differentiation has advanced considerably in recent years, a majority of 46,XY gonadal dysgenesis patients still cannot be provided with an accurate diagnosis. Some of these unexplained DSD cases may be due to mutations in novel DSD genes or genomic rearrangements affecting regulatory regions that lead to atypical gene expression. Here, we review our current knowledge of mammalian sex determination drawing on insights from human DSD patients and mouse models.
authors.affiliation: Murdoch Children's Research Institute, Royal Children's Hospital and Department of Paediatrics, The University of Melbourne, Melbourne, VIC, Australia.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Eggers
authors.forename: Andrew
authors.initials: A
authors.lastname: Sinclair
mesh_terms: D058531:46, XX Testicular Disorders of Sex Development / Q000235:genetics / Q000473:pathology; D000818:Animals; D058490:Disorder of Sex Development, 46,XY / Q000235:genetics* / Q000473:pathology; D050991:GATA4 Transcription Factor / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006066:Gonads / Q000254:growth & development / Q000473:pathology*; D006801:Humans; D048728:MAP Kinase Kinase Kinase 1 / Q000235:genetics / Q000378:metabolism; D020935:MAP Kinase Signaling System; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism; D012730:Sex Chromosomes / Q000235:genetics / Q000378:metabolism; D019849:Sex Determination Processes; D012733:Sex Differentiation; D054339:Steroidogenic Factor 1 / Q000235:genetics / Q000378:metabolism; D009396:Wilms Tumor / Q000235:genetics / Q000473:pathology
chemical_list: D050991:GATA4 Transcription Factor; C484170:GATA4 protein, human; D055748:SOXB1 Transcription Factors; C527786:Sox3 protein, mouse; D054339:Steroidogenic Factor 1; C515058:steroidogenic factor 1, mouse; D048728:MAP Kinase Kinase Kinase 1; C482576:MAP3K1 protein, human