Mutation of murine Sox4 untranslated regions results in partially penetrant perinatal lethality

In Vivo. 2014 Sep-Oct;28(5):709-18.

Abstract

Background: Sox4 is an essential gene, and genetic deletion results in embryonic lethality. In an effort to develop mice with tissue-specific deletion, we bred conditional knockout mice bearing LoxP recombination sites flanking the Sox4 gene, with the LoxP sites located in the Sox4 5'UTR and 3'UTR.

Results: The number of mice homozygous for this LoxP-flanked conditional knockout allele was far below the expected number, suggesting embryonic lethality with reduced penetrance. From over 200 animals bred, only 11% were homozygous Sox4(flox/flox) mice, compared to the expected Mendelian ratio of 25% (p<0.001). Moreover, there was a significant reduction in the number of female Sox4(flox/flox) mice (26%) relative to male Sox4(flox/flox) mice (p=0.0371). Reduced Sox4 expression in homozygous embryos was confirmed by in-situ hybridization and Quantitative real-time polymerase chain reaction (QPCR).

Conclusion: LoxP sites in the 5' and 3' UTR of both alleles of Sox4 resulted in reduced, but variable expression of Sox4 message.

Keywords: ISH; Mouse; Sox4; perinatal lethality; transcription.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Breeding
  • Cell Line
  • Embryo, Mammalian / metabolism
  • Female
  • Gene Expression
  • Gene Order
  • Gene Targeting
  • Genes, Lethal*
  • Genotype
  • Humans
  • Immunohistochemistry
  • Infant, Newborn
  • Mice
  • Mice, Transgenic
  • Mutation*
  • Penetrance*
  • Perinatal Death / etiology*
  • Phenotype
  • Pregnancy
  • RNA, Messenger / genetics
  • SOXC Transcription Factors / genetics*
  • Untranslated Regions*

Substances

  • RNA, Messenger
  • SOXC Transcription Factors
  • Untranslated Regions