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

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.