Selective requirement of myosin light chain 2v in embryonic heart function.
Two major myosin light chain 2 isoforms are coexpressed in the early stages of murine cardiogenesis, a cardiac ventricular isoform and a cardiac atrial isoform, each of which is tightly regulated in a muscle cell-type-specific manner during embryogenesis (Chien, K. R., Zhu, H., Knowlton, K. U., Miller-Hance, W., van Bilsen, M., O'Brien, T. X., and Evans, S. M. (1993) Annu. Rev. Physiol. 55, 77-95). We have disrupted myosin light chain 2v gene in mice and monitored in vivo cardiac function in living myosin light chain 2v -/- embryos. The mutant embryos die at approximately embryonic day 12.5. In mutant ventricles, the myosin light chain 2a protein level is increased and reaches levels comparable to the myosin light chain 2v in the ventricles of wild type littermates and is appropriately incorporated into the thick filaments of mutant embryonic hearts. However, despite the substitution of myosin light chain 2a, ultrastructural analysis revealed defects in sarcomeric assembly and an embryonic form of dilated cardiomyopathy characterized by a significantly reduced left ventricular ejection fraction in mutant embryos compared with wild type littermates. We conclude that myosin light chain 2v may have a unique function in the maintenance of cardiac contractility and ventricular chamber morphogenesis during mammalian cardiogenesis and that a chamber-specific combinatorial code for sarcomeric assembly may exist that ultimately requires myosin light chain 2v in ventricular muscle cells.
Chen
J
J
Department of Medicine, University of California at San Diego, School of Medicine, La Jolla, California 92093-0613, USA.
Kubalak
S W
SW
Minamisawa
S
S
Price
R L
RL
Becker
K D
KD
Hickey
R
R
Ross
J
J
Chien
K R
KR
D000818:Animals; D024722:Cardiac Myosins; D005260:Female; D006321:Heart / Q000196:embryology* / Q000502:physiology*; D008297:Male; D051379:Mice; D008854:Microscopy, Electron; D009206:Myocardium / Q000648:ultrastructure; D018994:Myosin Light Chains / Q000235:genetics / Q000378:metabolism*; D017354:Point Mutation; D011995:Recombination, Genetic
D018994:Myosin Light Chains; C107184:myosin light chain 2; D024722:Cardiac Myosins