Homozygous CREM-IbΔC-X Overexpressing Mice Are a Reliable and Effective Disease Model for Atrial Fibrillation

Frontiers in Pharmacology
Frank T StümpelFrank U Müller

Abstract

Background: Atrial fibrillation (AF) is a significant cause of morbidity and mortality with foreseeably increasing prevalence. While large animal models of the disease are well established but resource intensive, transgenic AF mouse models are not yet widely used to develop or validate novel therapeutics for AF. Hemizygous mice with a cardiomyocyte-specific overexpression of the human cAMP response element modulator (CREM) isoform IbΔC-X spontaneously develop AF on grounds of an arrhythmogenic substrate consisting of alterations in structure, conduction, and calcium handling. Objective: We investigated if homozygous expression of the CREM-IbΔC-X transgene in mice alters the time course of AF development, and if homozygous CREM-IbΔC-X transgenics could be suitable as a disease model of AF. Methods: Southern Blot, quantitative real-time PCR, and immunoblotting were used to identify and verify homozygous transgenics. Cardiac gravimetry, quantitative real-time RT-PCR, histology, survival analysis, and repeated ECG recordings allowed assessment of phenotypic development and effects of antiarrhythmic drugs. Results: Homozygous animals could be identified by Southern blot and quantitative PCR, showing a strong trend to increased trans...Continue Reading

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Citations

Feb 18, 2020·Progress in Biophysics and Molecular Biology·M ScardigliC Ferrantini
May 1, 2021·International Journal of Molecular Sciences·Gerhild EulerMariana S Parahuleva
May 19, 2021·Pflügers Archiv : European journal of physiology·Wenli DaiChristopher R Weber

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Methods Mentioned

BETA
transgenic
transgenics
PCR
light microscopy

Software Mentioned

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NIS
Pro Plus
REST
SigmaStat
LabChart Pro
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