A transgenic bacterial artificial chromosome approach to identify regulatory regions that direct and expression in Müllerian duct mesenchyme.

A transgenic mouse approach using bacterial artificial chromosomes (BAC) was used to identify regulatory regions that direct Müllerian duct expression for and (, also known as ). encodes the receptor that mediates anti-Müllerian hormone (AMH) signaling for Müllerian duct regression in male embryos. is expressed in the Müllerian duct mesenchyme of both male and female embryos. A ∼147-kb BAC clone containing the locus was used to generate transgenic mice. The transgene was able to rescue the block in Müllerian duct regression of -null males, suggesting that the BAC clone contains regulatory sequences active in male embryos. is expressed in the developing skeleton of male and female embryos but is also an AMH-induced gene that is expressed in the Müllerian duct mesenchyme exclusively in male embryos. transgenic mice were previously generated using a ∼204-kb BAC clone. Crosses of mice to Cre-dependent reporter mice resulted in reporter expression in the developing skeleton and in the Müllerian duct mesenchyme of male but not female embryos. transgenic mice were previously generated using a 39-kb genomic region surrounding the locus. embryos expressed red fluorescence in the developing skeleton and Müllerian duct mesenchyme of male but not female embryos. In addition, female embryos ectopically expressing human AMH from an transgene activated red fluorescence in the Müllerian duct mesenchyme. These results suggest that the 39-kb region used to generate contains male-specific Müllerian duct mesenchyme regulatory sequences that are responsive to AMH signaling. These BAC transgenic mouse approaches identify two distinct regions that direct Müllerian duct mesenchyme expression and contribute fundamental knowledge to define a gene regulatory network for sex differentiation.