Y Chromosome Short Arm-Sxr Recombination in XSxr/Y Males Causes Deletion of Rbm and XY Female Sex Reversal

• Published in: Proceedings of the National Academy of Sciences - PNAS 1995-10, Vol.92 (22), p.10403-10407
• Main Authors: Laval, Steven H., Glenister, Peter H., Rasberry, Carol, Thornton, Claire E., Mahadevaiah, Shantha K., Cooke, Howard J., Burgoyne, Paul S., Cattanach, Bruce M.
• Format: Article
• Language: English
• Subjects: Animals; Base Sequence; Biological Evolution; Blotting, Southern; Chromosome Mapping; Disorders of Sex Development; DNA Primers; DNA-Binding Proteins - genetics; Female; Female animals; Gene Deletion; Genes; Genetic Carrier Screening; Genetic loci; Genetic Variation; Genetics; Humans; Hypoxanthine Phosphoribosyltransferase - genetics; Male; Male animals; Mice; Mice, Inbred AKR; Molecular Sequence Data; Multigene Family; Mus musculus domesticus; Nuclear Proteins; Polymerase Chain Reaction; Recombination, Genetic; Restriction Mapping; Reverse transcriptase polymerase chain reaction; Sex chromosomes; Sex reversal surgery; Sex-Determining Region Y Protein; Testes; Testis - metabolism; Transcription Factors; X Chromosome; Y Chromosome
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.92.22.10403

We earlier described three lines of sex-reversed XY female mice deleted for sequences believed close to the testes-determining gene (Sry) on the Y chromosome short arm (Yp). The original sex-reversed females appeared among the offspring of XY males that carried the Yp duplication Sxr on their X chromosome. Earlier cytogenetic observations had suggested that the deletions resulted from asymmetrical meiotic recombination 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 domesticus 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 established that Rbm, the murine homologue of a gene family cloned from the human Y chromosome, lies between Sry and the centromere. Analysis of two additional XY female lines shows that asymmetrical Yp-Sxr recombination leading to XY female sex reversal results in deletion of Rbm sequences. The deletions bring Sry closer to Y centromere, consistent with the hypothesis that position-effect inactivation of Sry is the basis for the sex reversal.