Two genes substitute for the mouse Y chromosome for spermatogenesis and reproduction

Science. 2016 Jan 29;351(6272):514-6. doi: 10.1126/science.aad1795.


The mammalian Y chromosome is considered a symbol of maleness, as it encodes a gene driving male sex determination, Sry, as well as a battery of other genes important for male reproduction. We previously demonstrated in the mouse that successful assisted reproduction can be achieved when the Y gene contribution is limited to only two genes, Sry and spermatogonial proliferation factor Eif2s3y. Here, we replaced Sry by transgenic activation of its downstream target Sox9, and Eif2s3y, by transgenic overexpression of its X chromosome-encoded homolog Eif2s3x. The resulting males with no Y chromosome genes produced haploid male gametes and sired offspring after assisted reproduction. Our findings support the existence of functional redundancy between the Y chromosome genes and their homologs encoded on other chromosomes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Eukaryotic Initiation Factor-2 / genetics*
  • Female
  • Gene Dosage
  • Haploidy
  • Male
  • Mice
  • Mice, Transgenic
  • Reproductive Techniques, Assisted
  • SOX9 Transcription Factor / genetics*
  • Sex-Determining Region Y Protein / genetics*
  • Spermatogenesis / genetics*
  • Spermatogonia / cytology
  • Spermatogonia / metabolism
  • X Chromosome / genetics*
  • Y Chromosome / genetics*


  • Eukaryotic Initiation Factor-2
  • SOX9 Transcription Factor
  • Sex-Determining Region Y Protein
  • Sox9 protein, mouse
  • Sry protein, mouse