Y-CHROMOSOME SHORT ARM-SXR RECOMBINATION IN XSXR Y MALES CAUSES DELETION OF RBM AND XY FEMALE SEX REVERSAL/

We earlier described three lines of sex-reversed XY female mice delete d for sequences believed close to the testes-determining gene (Sry) on the Y chromosome short arm (Yp). The original sex-reversed females ap peared among the offspring of XY males that carried the Yp duplication Sxr on their X chromosome. Earlier cytogenetic observations had sugge sted that the deletions resulted from asymmetrical meiotic recombinati on between the Y and the homologous Sxr region, but no direct evidence for this hypothesis was available. We have now analyzed the offspring of XSxr/Y males carrying an evolutionarily divergent Mus musculus dom esticus Y chromosome, which permits detection and characterization of such recombination events. This analysis has enabled the derivation of a recombination map of Yp and Sxr, also demonstrating the orientation of Yp with respect to the Y centromere. The mapping data have establi shed that Rbm, the murine homologue of a gene family cloned from the h uman Y chromosome, lies between Sry and the centromere. Analysis of tw o additional XY female lines shows that asymmetrical Yp-Sxr recombinat ion leading to XY female sex reversal results in deletion of Rbm seque nces. The deletions bring Sry closer to Y centromere, consistent with the hypothesis that position-effect inactivation of Sry is the basis f or the sex reversal.