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

Gillet, Ludovic; Guichard, Sabrina; Essers, Maria C.; Rougier, Jean-Sébastien; Abriel, Hugues (2019). Dystrophin and calcium current are decreased in cardiomyocytes expressing Cre enzyme driven by αMHC but not TNT promoter. Scientific reports, 9(1), p. 19422. Springer Nature 10.1038/s41598-019-55950-w

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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 (Cav1.2) and sodium (Nav1.5) 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, Nav1.5 expression, and Cav1.2 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 (ICaL), but not Nav1.5 protein expression was altered in those mice. Surprisingly, in hearts from 12-week-old and older TNT-Cre+ mice, neither ICaL nor dystrophin and Nav1.5 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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Biochemistry and Molecular Medicine

UniBE Contributor:

Guichard, Sabrina Lucienne Anny; Essers, Maria Cristina; Rougier, Jean-Sébastien and Abriel, Hugues

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

2045-2322

Publisher:

Springer Nature

Language:

English

Submitter:

Kevin Marc Rupp

Date Deposited:

23 Jan 2020 12:35

Last Modified:

26 Jan 2020 02:49

Publisher DOI:

10.1038/s41598-019-55950-w

PubMed ID:

31857666

BORIS DOI:

10.7892/boris.138158

URI:

https://boris.unibe.ch/id/eprint/138158

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