Hemizygous Le-Cre transgenic mice have severe eye abnormalities on some genetic backgrounds in the absence of LoxPSites

Natalie J. Dorà*, J. Martin Collinson, Robert E. Hill, John D. West

*Corresponding author for this work

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Eye phenotypes were investigated in Le-CreTg/-; Pax6fl/+ mice, which were expected to show tissue-specific reduction of Pax6 in surface ectoderm derivatives. To provide a better comparison with our previous studies of Pax6+/- eye phenotypes, hemizygous Le-CreTg/- and heterozygous Pax6fl/+ mice were crossed onto the CBA/Ca genetic background. After the Le-Cre transgene had been backcrossed to CBA/Ca for seven generations, significant eye abnormalities occurred in some hemizygous Le-CreTg/-; Pax6+/+ controls (without a floxed Pax6fl allele) as well as experimental Le-CreTg/-; Pax6fl/+ mice. However, no abnormalities were seen in Le-Cre-/-; Pax6fl/+ or Le-Cre-/-; Pax6+/+ controls (without the Le-Cre transgene). The severity and frequency of the eye abnormalities in Le-CreTg/-; Pax6+/+ control mice diminished after backcrossing Le-CreTg/- mice to the original FVB/N strain for two generations, showing that the effect was reversible. This genetic background effect suggests that the eye abnormalities are a consequence of an interaction between the Le-Cre transgene and alleles of unknown modifier genes present in certain genetic backgrounds. The abnormalities were also ameliorated by introducing additional Pax6 gene copies on a CBA/Ca background, suggesting involvement of Pax6 depletion in Le-CreTg/-; Pax6+/+ mice rather than direct action of Cre recombinase on cryptic pseudo-loxP sites. One possibility is that expression of Cre recombinase from the Pax6-Le regulatory sequences in the Le-Cre transgene depletes cofactors required for endogenous Pax6 gene expression. Our observation that eye abnormalities can occur in hemizygous Le-CreTg/-; Pax6+/+ mice, in the absence of a floxed allele, demonstrates the importance of including all the relevant genetic controls in Cre-loxP experiments.

Original languageEnglish
Article number109193
Pages (from-to)1-19
Number of pages19
JournalPloS ONE
Volume9
Issue number10
DOIs
Publication statusPublished - 1 Oct 2014

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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