© The Rockefeller University Press,
0021-9525/1998//943 $5.00
The Journal of Cell Biology, Volume 141, Number 4,
, 1998 943-953
Myosin Heavy Chains IIa and IId Are Functionally Distinct in the Mouse
Carol A. Sartorius
,
Brian D. Lu*,
Leslie Acakpo-Satchivi
,
Renee P. Jacobsen
,
William C. Byrnes||, and
Leslie A. Leinwand
* Department of Microbiology and Immunology,
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.

CiteULike
Complore
Connotea
Del.icio.us
Digg
Facebook
Reddit
Technorati
Twitter What's this?
This article has been cited by other articles:
-
Gokhin, D. S., Ward, S. R., Bremner, S. N., Lieber, R. L.
(2008). Quantitative analysis of neonatal skeletal muscle functional improvement in the mouse. J. Exp. Biol.
211: 837-843
[Abstract]
[Full Text]
-
Ji, J., Tsika, G. L., Rindt, H., Schreiber, K. L., McCarthy, J. J., Kelm, R. J. Jr., Tsika, R.
(2007). Pur{alpha} and Pur{beta} Collaborate with Sp3 To Negatively Regulate {beta}-Myosin Heavy Chain Gene Expression during Skeletal Muscle Inactivity. Mol. Cell. Biol.
27: 1531-1543
[Abstract]
[Full Text]
-
Dapp, C., Schmutz, S., Hoppeler, H., Fluck, M.
(2004). Transcriptional reprogramming and ultrastructure during atrophy and recovery of mouse soleus muscle. Physiol. Genomics
20: 97-107
[Abstract]
[Full Text]
-
Rudolf, R., Mongillo, M., Magalhaes, P. J., Pozzan, T.
(2004). In vivo monitoring of Ca2+ uptake into mitochondria of mouse skeletal muscle during contraction. JCB
166: 527-536
[Abstract]
[Full Text]
-
Jin, T.-E., Witzemann, V., Brecht, M.
(2004). Fiber Types of the Intrinsic Whisker Muscle and Whisking Behavior. J. Neurosci.
24: 3386-3393
[Abstract]
[Full Text]
-
Karasseva, N., Tsika, G., Ji, J., Zhang, A., Mao, X., Tsika, R.
(2003). Transcription Enhancer Factor 1 Binds Multiple Muscle MEF2 and A/T-Rich Elements during Fast-to-Slow Skeletal Muscle Fiber Type Transitions. Mol. Cell. Biol.
23: 5143-5164
[Abstract]
[Full Text]
-
Suwa, M., Nakano, H., Higaki, Y., Nakamura, T., Katsuta, S., Kumagai, S.
(2003). Increased wheel-running activity in the genetically skeletal muscle fast-twitch fiber-dominant rats. J. Appl. Physiol.
94: 185-192
[Abstract]
[Full Text]
-
Widmer, C.G., Morris-Wiman, J.A., Nekula, C.
(2002). Spatial Distribution of Myosin Heavy-chain Isoforms in Mouse Masseter. JDR
81: 33-38
[Abstract]
[Full Text]
-
Allen, D. L., Harrison, B. C., Sartorius, C., Byrnes, W. C., Leinwand, L. A.
(2001). Mutation of the IIB myosin heavy chain gene results in muscle fiber loss and compensatory hypertrophy. Am. J. Physiol. Cell Physiol.
280: C637-C645
[Abstract]
[Full Text]
-
Rafael, J. A., Townsend, E. R., Squire, S. E., Potter, A. C., Chamberlain, J. S., Davies, K. E.
(2000). Dystrophin and utrophin influence fiber type composition and post-synaptic membrane structure. Hum Mol Genet
9: 1357-1367
[Abstract]
[Full Text]
-
Vyas, D. R., McCarthy, J. J., Tsika, R. W.
(1999). Nuclear Protein Binding at the beta -Myosin Heavy Chain A/T-rich Element Is Enriched following Increased Skeletal Muscle Activity. J. Biol. Chem.
274: 30832-30842
[Abstract]
[Full Text]
-
Weiss, A., McDonough, D., Wertman, B., Acakpo-Satchivi, L., Montgomery, K., Kucherlapati, R., Leinwand, L., Krauter, K.
(1999). Organization of human and mouse skeletal myosin heavy chain gene clusters is highly conserved. Proc. Natl. Acad. Sci. USA
96: 2958-2963
[Abstract]
[Full Text]