The mouse locus harbors a cryptic exon that is essential for male sex determination.

The mammalian sex-determining gene induces male development. Since its discovery 30 years ago, has been believed to be a single-exon gene. Here, we identified a cryptic second exon of mouse and a corresponding two-exon type () transcript. XY mice lacking were sex-reversed, and ectopic expression of in XX mice induced male development. messenger RNA is expressed similarly to that of canonical single-exon type (), but SRY-T protein is expressed predominantly because of the absence of a degron in the C terminus of SRY-S. exon2 appears to have evolved recently in mice through acquisition of a retrotransposon-derived coding sequence to replace the degron. Our findings suggest that in nature, SRY-T, not SRY-S, is the bona fide testis-determining factor.