Sex determination: a 'window' of DAX1 activity.
Traditionally, DAX1 was considered an 'anti-testis' gene because DAX1 duplications in XY individuals cause male-to-female sex reversal: dosage-sensitive sex reversal (DSS). In DSS, two active DAX1 genes on one X chromosome can abrogate testis formation. By contrast, mutations and deletions of DAX1 cause adrenal hypoplasia congenita (AHC). Although AHC patients develop testes, gonadal defects include disorganized testis cords and hypogonadotropic hypogonadism, which is not completely restored with gonadotropin or androgen therapy. Recent evidence of XY sex reversal in Dax1-deficient mice strongly supports a role for Dax1 as a 'pro-testis' gene. Therefore, perhaps DAX1/Dax1 acts within a 'window' of activity, outside of which testis formation does not occur. Here, we discuss the function and possible mechanisms of DAX1 action in male gonadogenesis.
Ludbrook
Louisa M
LM
Prince Henry's Institute of Medical Research, PO Box 5152, Clayton, VIC 3168, Australia.
Harley
Vincent R
VR
D000818:Animals; D057137:DAX-1 Orphan Nuclear Receptor; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation / Q000502:physiology; D018168:Receptors, Retinoic Acid / Q000235:genetics* / Q000502:physiology; D012097:Repressor Proteins / Q000235:genetics* / Q000502:physiology; D019849:Sex Determination Processes; D012741:Sexual Maturation / Q000235:genetics; D013737:Testis / Q000254:growth & development / Q000502:physiology
D057137:DAX-1 Orphan Nuclear Receptor; D004268:DNA-Binding Proteins; C539965:NR0B1 protein, human; C539966:Nr0b1 protein, mouse; D018168:Receptors, Retinoic Acid; D012097:Repressor Proteins