THE GENETIC-BASIS OF MURINE AND HUMAN SEX DETERMINATION - A REVIEW

Determination of mammalian sex depends on the presence or absence of a functional testis. Testes are determined by the activity of the testi s determining factor encoded by the sex determining gene, Y (SRY) loca ted on the Y chromosome. Considerable evidence suggests that the SRY g ene is the only gene on the Y chromosome that is both necessary and su fficient to initiate testis determination. Other steps in the mammalia n sex determining pathway are unknown, although recent advances have s hown that mutations in X chromosome and autosomal loci are also associ ated with sex reversal, suggesting the presence of at least one other sex determining gene. Duplications of sequences on the short arm of th e human X chromosome, including the DAX-1 (DSS-AHC critical region on the X chromosome, gene 1) gene, are occasionally associated with XY ma le-to-female sex reversal. In addition, mutations in the SRY-related g ene SOX9 (SRY-related box) are associated with a failure of human test icular determination. Furthermore, the occurrence of inherited sex rev ersed conditions in both mice and men indicate the presence of at leas t one other sex determining gene. Breeding the Y chromosome from certa in Mus musculus domesticus strains into the laboratory mouse strain C5 7BL/6J results in XY male-to-female sex reversal. This suggests both a llelic variation of the Sry gene and the presence of autosomal sex det ermining genes. In humans, familial cases of SRY-negative XX males occ ur. Analysis of the transmission of the trait indicates the segregatio n of an autosomal or X-linked recessive mutation. The mutation may be in a gene whose wild-type function is to inhibit male sex determinatio n. SRY may trigger male sex determination by repressing or functionall y antagonizing the product of this gene.