Sex Reversal Caused by Mus musculus domesticus Y Chromosomes Linked to Variant Expression of the Testis-Determining Gene Sry

Abstract

When the Y chromosomes from certain populations of Mus musculus domesticus are introduced into the mouse strain C57BL/6 (B6), testis determination can fail, resulting in gonads developing either as ovotestes (with both ovarian and testicular components) or as ovaries. Not all YDOM chromosomes cause sex reversal. YDOM chromosomes are divided into three classes based upon their ability to induce testes in B6. The molecular basis underlying the three YDOM classes is an enigma. The simplest explanation is that they harbor different alleles of the testis-determining gene, Sry. Sequencing of SryDOM genes has indeed identified polymorphisms. However, none were unequivocally linked to the sex-reversal trait. It was concluded that all SRYDOM proteins are functionally equivalent. Using a semiquantitative RT-PCR assay, we now show that representatives of the three YDOM classes have variant Sry expression patterns, that severity of sex reversal correlates with Sry mRNA titers, and that genetic correction of the sex reversal results in the upregulation of Sry expression. We propose that the variant Sry expression patterns result from polymorphisms at the site of a putative Sry enhancer.