DELETION OF Y-CHROMOSOME SEQUENCES LOCATED OUTSIDE THE TESTIS-DETERMINING REGION CAN CAUSE XY FEMALE SEX REVERSAL

An approach designed to map and generate mutations in the region of the short arm of the mouse Y chromosome, known to be involved in sex determination and spermatogenesis, is described. This relies on homologous Yp-Sxr(a) pairing and asymmetrical exchange which can occur at meiosis in XY males carrying Sxr(a) on their X chromosome. Such exchange potentially generates deficiencies and duplications of Yp or Sxr(a). Three fertile XY females were found out of about 450 XY offspring from XSxr(a)/Y x XX crosses. In all three, despite evidence for deletion of Y chromosomal material, the Sry locus was intact. Each deletion involved a repeat sequence, Sx1, located at a distance from Sry. Since expression of Sry was affected these results suggest that long range position effects have disrupted Sry action.