Serological evidence for H–Y antigen in Sxr, XX sex-reversed phenotypic males

Abstract

IT is generally considered that the Y chromosome is necessary for the development of the mammalian testis and the consequent male phenotype. Exceptions occasionally occur in man and other animals, where a male phenotype is associated with an apparently normal female karyotype. In some instances it has been possible to show that such “sex reversal” has an autosomal genetic basis. Although this might imply that the Y chromosome is not a prerequisite of maleness, it has not been excluded that a small male-determining region of the Y may have been translocated to an autosome without producing a recognisable karyotypic change¹ (reviewed in ref. 2). The best studied case of male development with an apparently female karyotype is provided by the Sxr mutant in the mouse. This autosomal dominant condition causes both XX and XO mice to develop as males, although germ cells are absent in Sxr,XX animals and spermatogenesis is impaired in Sxr,XO mice. Sxr,XY males have a slightly reduced testis size but are usually fertile. Cytological scrutiny of mitotic and meiotic chromosomes (including chromosome banding) has revealed no evidence for a Y–autosome translocation, although a small translocation undetectable by the methods used cannot be ruled out (reviewed in ref. 2). This situation can now be investigated using serological methods for detecting H–Y (histocompatibility–Y) antigen on the surface of mouse sperm³ and male epidermal cells⁴. These techniques have provided further evidence that expression of this antigen is governed by a gene (or genes) on the Y chromosome even in the absence of the normal male phenotype⁵. Thus, serological demonstration of H–Y antigen offers a non-karyological criterion for the presence of a translocated portion of the Y in Sxr,XX males, because their cells should express H–Y if Sxr is a translocation involving the H–Y genetic determinant. We report here that Sxr,XX males express H–Y to a degree that may be the same or slightly lower than that of normal males, and that their Sxr,XY siblings seem to have near-normal levels of H–Y. The simplest explanation is that male-determining and H–Y-determining portions of the Y chromosome are present in the animals carrying Sxr.