Functional equivalence of the SOX2 and SOX3 transcription factors in the developing mouse brain and testes

Fatwa Adikusuma, Daniel Pederick, Dale McAninch, James Hughes, Paul Thomas

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)


Gene duplication provides spare genetic material that evolution can craft into new functions. Sox2 and Sox3 are evolutionarily related genes with overlapping and unique sites of expression during embryogenesis. It is currently unclear whether SOX2 and SOX3 have identical or different functions. Here, we use CRISPR/Cas9-assisted mutagenesis to perform a gene-swap, replacing the Sox3 ORF with the Sox2 ORF to investigate their functional equivalence in the brain and testes. We show that increased expression of SOX2 can functionally replace SOX3 in the development of the infundibular recess/ventral diencephalon, and largely rescues pituitary gland defects that occur in Sox3 null mice. We also show that ectopic expression of SOX2 in the testes functionally rescues the spermatogenic defect of Sox3 null mice, and restores gene expression to near normal levels. Together, these in vivo data provide strong evidence that SOX2 and SOX3 proteins are functionally equivalent.

Original languageEnglish
Pages (from-to)1495-1503
Number of pages9
Issue number3
Publication statusPublished or Issued - Jul 2017


  • CRISPR/CAS9 mutagenesis
  • Gene swap
  • SOXB1 genes

ASJC Scopus subject areas

  • Genetics

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