In Vivo Elongation of Thin Filaments Results in Heart Failure

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2020 Jan 4

PMID 31899774

Citations 10

Authors

Lei Mi-Mi

Gerrie P Farman

Rachel M Mayfield

Joshua Strom

Miensheng Chu

Christopher T Pappas

Carol C Gregorio

Affiliations

Soon will be listed here.

Abstract

A novel cardiac-specific transgenic mouse model was generated to identify the physiological consequences of elongated thin filaments during post-natal development in the heart. Remarkably, increasing the expression levels in vivo of just one sarcomeric protein, Lmod2, results in ~10% longer thin filaments (up to 26% longer in some individual sarcomeres) that produce up to 50% less contractile force. Increasing the levels of Lmod2 in vivo (Lmod2-TG) also allows us to probe the contribution of Lmod2 in the progression of cardiac myopathy because Lmod2-TG mice present with a unique cardiomyopathy involving enlarged atrial and ventricular lumens, increased heart mass, disorganized myofibrils and eventually, heart failure. Turning off of Lmod2 transgene expression at postnatal day 3 successfully prevents thin filament elongation, as well as gross morphological and functional disease progression. We show here that Lmod2 has an essential role in regulating cardiac contractile force and function.

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