Absence of extraocular muscle pathology in Duchenne's muscular dystrophy: role for calcium homeostasis in extraocular muscle sparing

doi:10.1084/jem.182.2.467

This Article

	Full Text (PDF)
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JEM
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Khurana, T. S.
	Articles by Kunkel, L. M.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Khurana, T. S.
	Articles by Kunkel, L. M.


Social Bookmarking

	What's this?

ARTICLES

Absence of extraocular muscle pathology in Duchenne's muscular dystrophy: role for calcium homeostasis in extraocular muscle sparing

TS Khurana, RA Prendergast, HS Alameddine, FM Tome, M Fardeau, K Arahata, H Sugita and LM Kunkel
Howard Hughes Medical Institute, Division of Genetics, Children's Hospital, Boston, Massachusetts 02115, USA.

Duchenne muscular dystrophy (DMD) is characterized by clinical weakness and progressive necrosis of striated muscle as a consequence of dystrophin deficiency. While all skeletal muscle groups are thought to be affected, enigmatically, the extraocular muscles (EOM) appear clinically unaffected. Here we show that dystrophin deficiency does not result in myonecrosis or pathologically elevated levels of intracellular calcium ([Ca2+]i) in EOM. At variance with a previous report, we find no evidence for dystrophin-related protein/utrophin up- regulation in EOM. In vitro experiments demonstrate that extraocular muscles are inherently more resistant to necrosis caused by pharmacologically elevated [Ca2+]i levels when compared with pectoral musculature. We believe that EOM are spared in DMD because of their intrinsic ability to maintain calcium homeostasis better than other striated muscle groups. Our results indicate that modulating levels of [Ca2+]i in muscle may be of potential therapeutic use in DMD.
Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Add to Reddit Reddit Add to Technorati Technorati What's this?

This article has been cited by other articles:

Thomas, L. B., Joseph, G. L., Adkins, T. D., Andrade, F. H., Stemple, J. C. (2008). Laryngeal Muscles Are Spared in the Dystrophin Deficient mdx Mouse. JSLHR 51: 586-595 [Abstract] [Full Text]
Wiesen, M. H. J., Bogdanovich, S., Agarkova, I., Perriard, J.-C., Khurana, T. S. (2007). Identification and Characterization of Layer-Specific Differences in Extraocular Muscle M-Bands. IOVS 48: 1119-1127 [Abstract] [Full Text]
Kleopa, K. A., Drousiotou, A., Mavrikiou, E., Ormiston, A., Kyriakides, T. (2006). Naturally occurring utrophin correlates with disease severity in Duchenne muscular dystrophy. Hum Mol Genet 15: 1623-1628 [Abstract] [Full Text]
Porter, J. D., Israel, S., Gong, B., Merriam, A. P., Feuerman, J., Khanna, S., Kaminski, H. J. (2006). Distinctive morphological and gene/protein expression signatures during myogenesis in novel cell lines from extraocular and hindlimb muscle. Physiol. Genomics 24: 264-275 [Abstract] [Full Text]
Fischer, M. D., Budak, M. T., Bakay, M., Gorospe, J. R., Kjellgren, D., Pedrosa-Domellof, F., Hoffman, E. P., Khurana, T. S. (2005). Definition of the unique human extraocular muscle allotype by expression profiling. Physiol. Genomics 22: 283-291 [Abstract] [Full Text]
Demoule, A., Divangahi, M., Danialou, G., Gvozdic, D., Larkin, G., Bao, W., Petrof, B. J. (2005). Expression and Regulation of CC Class Chemokines in the Dystrophic (mdx) Diaphragm. Am. J. Respir. Cell Mol. Bio. 33: 178-185 [Abstract] [Full Text]
Cheng, G., Merriam, A. P., Gong, B., Leahy, P., Khanna, S., Porter, J. D. (2004). Conserved and muscle-group-specific gene expression patterns shape postnatal development of the novel extraocular muscle phenotype. Physiol. Genomics 18: 184-195 [Abstract] [Full Text]
Porter, J. D., Merriam, A. P., Leahy, P., Gong, B., Feuerman, J., Cheng, G., Khanna, S. (2004). Temporal gene expression profiling of dystrophin-deficient (mdx) mouse diaphragm identifies conserved and muscle group-specific mechanisms in the pathogenesis of muscular dystrophy. Hum Mol Genet 13: 257-269 [Abstract] [Full Text]
Porter, J. D., Merriam, A. P., Gong, B., Kasturi, S., Zhou, X., Hauser, K. F., Andrade, F. H., Cheng, G. (2003). Postnatal suppression of myomesin, muscle creatine kinase and the M-line in rat extraocular muscle. J. Exp. Biol. 206: 3101-3112 [Abstract] [Full Text]
Porter, J. D., Merriam, A. P., Leahy, P., Gong, B., Khanna, S. (2003). Dissection of temporal gene expression signatures of affected and spared muscle groups in dystrophin-deficient (mdx) mice. Hum Mol Genet 12: 1813-1821 [Abstract] [Full Text]
Khanna, S., Richmonds, C. R., Kaminski, H. J., Porter, J. D. (2003). Molecular Organization of the Extraocular Muscle Neuromuscular Junction: Partial Conservation of and Divergence from the Skeletal Muscle Prototype. IOVS 44: 1918-1926 [Abstract] [Full Text]
McLoon, L. K., Wirtschafter, J. (2003). Activated Satellite Cells in Extraocular Muscles of Normal Adult Monkeys and Humans. IOVS 44: 1927-1932 [Abstract] [Full Text]
Fischer, M. D., Gorospe, J. R., Felder, E., Bogdanovich, S., Pedrosa-Domellof, F., Ahima, R. S., Rubinstein, N. A., Hoffman, E. P., Khurana, T. S. (2002). Expression profiling reveals metabolic and structural components of extraocular muscles. Physiol. Genomics 9: 71-84 [Abstract] [Full Text]
Cheng, G., Porter, J. D. (2002). Transcriptional Profile of Rat Extraocular Muscle by Serial Analysis of Gene Expression. IOVS 43: 1048-1058 [Abstract] [Full Text]
Berchtold, M. W., Brinkmeier, H., Muntener, M. (2000). Calcium Ion in Skeletal Muscle: Its Crucial Role for Muscle Function, Plasticity, and Disease. Physiol. Rev. 80: 1215-1265 [Abstract] [Full Text]
Porter, J., Rafael, J., Ragusa, R., Brueckner, J., Trickett, J., Davies, K. (1998). The sparing of extraocular muscle in dystrophinopathy is lost in mice lacking utrophin and dystrophin. J. Cell Sci. 111: 1801-1811 [Abstract]