Farman, Gerrie P
Mayfield, Rachel M
Pappas, Christopher T
Gregorio, Carol C
AffiliationUniv Arizona, Dept Cellular & Mol Med
Univ Arizona, Sarver Mol Cardiovasc Res Program
MetadataShow full item record
PublisherPUBLIC LIBRARY SCIENCE
CitationMi-Mi L, Farman GP, Mayfield RM, Strom J, Chu M, Pappas CT, et al. (2020) In vivo elongation of thin filaments results in heart failure. PLoS ONE 15(1): e0226138. https://doi.org/ 10.1371/journal.pone.0226138
RightsCopyright © 2020 Mi-Mi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
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AbstractA 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 similar to 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.
NoteOpen access journal
VersionFinal published version
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