Cardiac-specific knockout of Lmod2 results in a severe reduction in myofilament force production and rapid cardiac failure
| Autor: | John P. Konhilas, Gerrie P. Farman, Rachel M. Mayfield, Christopher T. Pappas, Carol C. Gregorio |
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| Rok vydání: | 2018 |
| Předmět: |
Sarcomeres
0301 basic medicine Cardiac function curve Myofilament Contraction (grammar) Cardiomyopathy Muscle Proteins macromolecular substances Sarcomere Article Gene Knockout Techniques Mice Ventricular Dysfunction Left 03 medical and health sciences Myofibrils medicine Animals Myocytes Cardiac Molecular Biology Actin Heart Failure Mice Knockout Analysis of Variance Chemistry medicine.disease Cell biology Mice Inbred C57BL Cytoskeletal Proteins 030104 developmental biology Echocardiography Heart failure Knockout mouse Linear Models Calcium Cardiology and Cardiovascular Medicine Muscle Contraction |
| Zdroj: | Journal of Molecular and Cellular Cardiology. 122:88-97 |
| ISSN: | 0022-2828 |
| Popis: | Leiomodin-2 (Lmod2) is a striated muscle-specific actin binding protein that is implicated in assembly of thin filaments. The necessity of Lmod2 in the adult mouse and role it plays in the mechanics of contraction are unknown. To answer these questions, we generated cardiac-specific conditional Lmod2 knockout mice (cKO). These mice die within a week of induction of the knockout with severe left ventricular systolic dysfunction and little change in cardiac morphology. Cardiac trabeculae isolated from cKO mice have a significant decrease in maximum force production and a blunting of myofilament length-dependent activation. Thin filaments are non-uniform and substantially reduced in length in cKO hearts, affecting the functional overlap of the thick and thin filaments. Remarkably, we also found that Lmod2 levels are directly linked to thin filament length and cardiac function in vivo, with a low amount ( |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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