When Cre-mediated recombination in mice does not result in protein loss

Kirsten A. Turlo, Sean D. Gallaher, Roshni Vora, Frank A. Laski, M. Luisa Iruela-Arispe

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Cre/loxP recombination enables cellular specificity and, in the case of inducible systems, temporal control of genomic deletions. Here we used a SM22a tamoxifen-inducible Cre line to inactivate β1 integrin in adult smooth muscle. Interestingly, analysis of two distinct β1 loxP transgenic mice revealed vastly different outcomes after b1 integrin deletion. Lethality occurred 4 weeks postinduction in one Cre/loxP line, while no apparent phenotype was seen in the other line. Genetic analysis revealed appropriate DNA excision in both cases; however, differences were found in the degree of protein loss with absolutely no change in protein levels in the model that lacked a phenotype. Seeking to understand protein persistence despite appropriate recombination, we first validated the flox allele using a constitutive Cre line and demonstrated its ability to mediate effective protein inactivation. We then examined the possibility of heterozygous cell selection, protein turnover, and deletion efficiency with no success for explaining the phenotype. Finally, we documented the presence of the Cre-recombination episomal product, which persisted in tissue samples with no protein loss. The product was only noted in cells with low proliferative capacity. These findings highlight the potential for protein expression from the products of Cre-recombinase excised genes, particularly when deletion occurs in low turnover populations.

Original languageEnglish (US)
Pages (from-to)959-967
Number of pages9
JournalGenetics
Volume186
Issue number3
DOIs
StatePublished - Nov 2010

ASJC Scopus subject areas

  • Genetics

Fingerprint Dive into the research topics of 'When Cre-mediated recombination in mice does not result in protein loss'. Together they form a unique fingerprint.

Cite this