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

Science. 2020 Oct 2;370(6512):121-124. doi: 10.1126/science.abb6430.


The mammalian sex-determining gene Sry induces male development. Since its discovery 30 years ago, Sry has been believed to be a single-exon gene. Here, we identified a cryptic second exon of mouse Sry and a corresponding two-exon type Sry (Sry-T) transcript. XY mice lacking Sry-T were sex-reversed, and ectopic expression of Sry-T in XX mice induced male development. Sry-T messenger RNA is expressed similarly to that of canonical single-exon type Sry (Sry-S), but SRY-T protein is expressed predominantly because of the absence of a degron in the C terminus of SRY-S. Sry 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CRISPR-Cas Systems
  • Exons*
  • Gene Editing
  • Genes, Essential*
  • Genetic Loci
  • Male
  • Mice
  • Mice, Transgenic
  • RNA, Untranslated / genetics
  • Sequence Deletion
  • Sex Determination Processes*
  • Sex-Determining Region Y Protein / genetics*
  • Transcription, Genetic


  • Gt(ROSA)26Sor non-coding RNA, mouse
  • RNA, Untranslated
  • Sex-Determining Region Y Protein
  • Sry protein, mouse