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© The Rockefeller University Press, 0021-9525/1998//943 $5.00
The Journal of Cell Biology, Volume 141, Number 4, , 1998 943-953


Articles

Myosin Heavy Chains IIa and IId Are Functionally Distinct in the Mouse



Carol A. Sartorius§, Brian D. Lu*, Leslie Acakpo-Satchivi{ddagger}, Renee P. Jacobsen§, William C. Byrnes||, and Leslie A. Leinwand§

* Department of Microbiology and Immunology, {ddagger} Department of Molecular Genetics, Albert Einstein College of Medicine, New York 10461; and § Department of Molecular, Cellular, and Developmental Biology, || Department of Kinesiology, University of Colorado, Boulder, Colorado 80309

Myosin in adult murine skeletal muscle is composed primarily of three adult fast myosin heavy chain (MyHC) isoforms. These isoforms, MyHC-IIa, -IId, and -IIb, are >93% identical at the amino acid level and are broadly expressed in numerous muscles, and their genes are tightly linked. Mice with a null mutation in the MyHC-IId gene have phenotypes that include growth inhibition, muscle weakness, histological abnormalities, kyphosis (spinal curvature), and aberrant kinetics of muscle contraction and relaxation. Despite the lack of MyHC-IId, IId null mice have normal amounts of myosin in their muscles because of compensation by the MyHC-IIa gene. In each muscle examined from IId null mice, there was an increase in MyHC-IIa– containing fibers. MyHC-IIb content was unaffected in all muscles except the masseter, where its expression was extinguished in the IId null mice. Cross-sectional fiber areas, total muscle cross-sectional area, and total fiber number were affected in ways particular to each muscle. Developmental expression of adult MyHC genes remained unchanged in IId null mice. Despite this universal compensation of MyHC-IIa expression, IId null mice have severe phenotypes. We conclude that despite the similarity in sequence, MyHC-IIa and -IId have unique roles in the development and function of skeletal muscle.


Abbreviations used in this paper: CSA, cross-sectional area; dpc, days post-coitum; EDL, extensor digitorum longus; MyHC, myosin heavy chain; NADH-TR, NADH-tetrazolium reductase; RT, reverse transcription; TA, tibialis anterior.



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