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Vol. 273, Issue 2, 1252-1256, January 9, 1998
From the 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
Selective Requirement of Myosin Light Chain 2v in Embryonic Heart
Function
,,,,, and**
Department of Medicine and ** Center for
Molecular Genetics, University of California at San Diego, School of
Medicine, La Jolla, California 92093-0613, and § Department
of Cell Biology & Anatomy, Medical University of South Carolina,
Charleston, South Carolina 29425-2204, and ¶ Department of
Developmental Biology and Anatomy, School of Medicine, University of
South Carolina, Columbia, South Carolina 29208
/
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.
Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.
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