Monday Muscle Seminar M&Ms: Tom Cooper

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Mechanistic insights from modeling cardiac features of Myotonic Dystrophy, Type 1 in mice

Tom Cooper

Professor, Baylor College of Medicine, Houston, Texas, USA, Pathology and Immunology – Molecular and Cellular Biology – Molecular Physiology and Biophysics
R. Clarence and Irene H. Fulbright Chair in Pathology
S. Donald Greenberg Chair in Pathology


Myotonic dystrophy type 1 (DM1) is an autosomal dominant multisystemic disease caused by a CTG microsatellite repeat expansion in the DMPK gene, leading to the expression of pathogenic expanded CUG-repeat (CUGexp) containing RNA. The toxic CUGexp RNA causes disease by disrupting the activities of RNA binding proteins that regulate postnatal RNA processing ultimately resulting in expression of fetal protein isoforms of a subset of genes in adult tissues. Cardiac involvement affects 50% of individuals with DM1 primarily due to conduction abnormalities and arrhythmias causing 25% of disease-related deaths. We developed a transgenic mouse model for tetracycline-inducible and heart-specific expression of human DMPK mRNA containing 960 CUG repeats. CUGexp RNA is expressed in atria and ventricles and induced mice exhibit electrophysiological and molecular features of DM1 disease including cardiac conduction delays, spontaneous and inducible supraventricular arrhythmias, nuclear RNA foci with colocalization of the muscleblind RNA binding protein and alternative splicing defects. Importantly, both electrophysiological and molecular features were reversible upon loss of CUGexp RNA expression. The results identify potential mechanisms contributing to cardiac pathogenesis and demonstrate the utility of a reversible cardiac DM1 mouse model to facilitate development of targeted therapeutic approaches.

More information on Tom Cooper Lab’s webpage

Date : 7 juin 2021

Heure : 15h - 16h

Lieu: Visioconférence

Monday Muscle Seminar - M&M's

Tom Cooper