Male sexual differentiation in mice lacking H-Y antigen

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 XO 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 years and more recently a serologically detected antigen, also male-specific, has been reported. Those who believe that the two are antigenically distinct refer to the latter as SDM (serologically detected male) antigen, but many refer to both as H-Y antigen. The hypothesis that H-Y is itself the Y-dependent testis inducer, although supported by little or no direct evidence, 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.