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Dystrophin and calcium current are decreased in cardiomyocytes expressing Cre enzyme driven by ?MHC but not TNT promoter.

ABSTRACT: The Cre/lox system is a potent technology to control gene expression in mouse tissues. However, cardiac-specific Cre recombinase expression alone can lead to cardiac alterations when no loxP sites are present, which is not well understood. Many loxP-like sites have been identified in the mouse genome that might be Cre sensitive. One of them is located in the Dmd gene encoding dystrophin, a protein important for the function and stabilization of voltage-gated calcium (Ca_v1.2) and sodium (Na_v1.5) channels, respectively. Here, we investigate whether Cre affects dystrophin expression and function in hearts without loxP sites in the genome. In mice expressing Cre under the alpha-myosin heavy chain (MHC-Cre) or Troponin T (TNT-Cre) promoter, we investigated dystrophin expression, Na_v1.5 expression, and Ca_v1.2 function. Compared to age-matched MHC-Cre^- mice, dystrophin protein level was significantly decreased in hearts from MHC-Cre⁺ mice of more than 12-weeks-old. Quantitative RT-PCR revealed decreased mRNA levels of Dmd gene. Unexpectedly, calcium current (I_CaL), but not Na_v1.5 protein expression was altered in those mice. Surprisingly, in hearts from 12-week-old and older TNT-Cre⁺ mice, neither I_CaL nor dystrophin and Na_v1.5 protein content were altered compared to TNT-Cre^-. Cre recombinase unpredictably affects cardiac phenotype, and Cre-expressing mouse models should be carefully investigated before experimental use.

SUBMITTER: Gillet L

PROVIDER: S-EPMC6923407 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Dystrophin and calcium current are decreased in cardiomyocytes expressing Cre enzyme driven by αMHC but not TNT promoter.

Gillet Ludovic L Guichard Sabrina S Essers Maria C MC Rougier Jean-Sébastien JS Abriel Hugues H

Scientific reports 20191219 1

The Cre/lox system is a potent technology to control gene expression in mouse tissues. However, cardiac-specific Cre recombinase expression alone can lead to cardiac alterations when no loxP sites are present, which is not well understood. Many loxP-like sites have been identified in the mouse genome that might be Cre sensitive. One of them is located in the Dmd gene encoding dystrophin, a protein important for the function and stabilization of voltage-gated calcium (Ca<sub>v</sub>1.2) and sodiu ...[more]

PMID: 31857666

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Dataset Information

Dystrophin and calcium current are decreased in cardiomyocytes expressing Cre enzyme driven by ?MHC but not TNT promoter.

Publications

Dystrophin and calcium current are decreased in cardiomyocytes expressing Cre enzyme driven by αMHC but not TNT promoter.

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