Male sexual differentiation in mice lacking H–Y antigen

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Abstract
The sexual phenotype of an adult mammal depends on whether the fetal gonad has differentiated as a testis or as an ovary. Because individuals of XY or XXY sex chromosome constitution develop as males, while XX and X0 individuals develop as females, the presence of a Y chromosome seems normally to be required for testis differentiation and its absence to be necessary for differentiation of an ovary. The nature of the hypothetical Y-dependent substance responsible for masculinization of the indifferent gonad has been a matter for debate. A male-specific transplantation antigen, H–Y, has been known for many years1,2, and more recently a serologically detected antigen, also male-specific, has been reported3. Those who believe that the two are antigenically distinct4,5 refer to the latter as SDM (serologically detected male) antigen, but many refer to both as H–Y antigen6–8. The hypothesis9 that H–Y is itself the Y-dependent testis inducer, although supported by little or no direct evidence4,10, is economical and hence attractive. H–Y antigen is frequently stated to be the substance responsible for primary sex determination (for example, see ref. 11). We report here that H–Y is absent from certain mice that develop testes and are of indisputably male phenotype, hence this transplantation antigen is unlikely to be responsible for testis determination