Transferring the Y chromosome from M. d. poschiavinus (YPOS) into a C57BL/6J (B6) genetic background causes sex reversal. Half of the B6 XYPOS individuals are true hermaphrodites and half are phenotypic females. Although some B6 XYPOS hermaphrodites reproduce as males, B6 XYPOS females are sterile because most oocytes degenerate by 8-10 weeks of age. This aberrant sexual development is thought to arise because SryPOS, the Y-linked testis determining gene from M. d. poschiavinus, abnormally interacts with one or more B6 autosomal alleles involved in sex determination. To test the hypothesis that SryPOS causes germ cell death in B6 XYPOS females, germ cell development in B6 transgenic mice carrying SryPOS will be assessed by histological examination and fertility tests. In addition, to understand the molecular mechanism of Sry action, identification of the cell-specific expression of Sry is required. To this end, transgenic mice that carry a reporter gene (enhanced green fluorescent protein) under the control of Sry flanking/regulatory sequences will be used to identify specific somatic cells in developing fetal gonads that express Sry. Finally, I will test the hypothesis that the expression of anti-Mullerian hormone (Amh, a gene that is potentially downstream of Sry in the sexual differentiation pathway) causes germ cell death in B6 XYPOS females. B6 XYPOS fetuses will be tested for Amh and Amh Receptor expression by reverse transcription-polymerase chain reaction assays. Amh deficient B6 XYPOS mice (generated by mating F2 offspring from crosses between Amhtm1Bhr females and B6XYPOS hermaphrodites) will be analyzed by
