X-CHROMOSOME INACTIVATION DURING THE DEVELOPMENT OF THE MALE UROGENITAL RIDGE OF THE MOUSE

In the mouse, the activity of Sry (sex-determining gene on the Y chrom osome) initiates the transformation of the indifferent gonad into a te stis. In humans, a partial Xp21 duplication leads to the development o f ovaries instead of testes in XY individuals. This observation indica tes that sex determination might also be influenced by a gene-dosage c ompensation mechanism, in addition to a dominant action of the Sry gen e. In female mammals, the regulation of X-linked gene dosage at early embryogenesis is achieved through the inactivation of one of the two X chromosomes. Here we have investigated the possibility that inactivat ion of the X chromosome may play a role in male sex determination. We have shown, using an X-linked lacZ transgenic mouse line, that loss of beta-galactosidase activity occurs in certain somatic cells of the de veloping male urogenital ridge. When changes associated with apoptosis of mesonephric tubules in the developing urogenital ridges are taken into account, expression of the Xist (X inactive specific transcript) gene correlates with X inactivation revealed by loss of beta-galactosi dase activity in very early mesonephric tubule epithelial cells, gonad al interstitial mesenchymal cells and coelomic epithelial cells.