Muscle degeneration without mechanical injury in sarcoglycan deficiency

In humans, mutations in the genes encoding components of the dystrophin–glycoprotein complex cause muscular dystrophy. Specifically, primary mutations in the genes encoding α-, β-, γ-, and δ-sarcoglycan have been identified in humans with limb-girdle muscular dystrophy. Mice lacking γ-sarcoglycan de...

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Prif Awduron: Hack, A. A., Cordier, L., Shoturma, D. I., Lam, M. Y., Sweeney, H. L., McNally, E. M.
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Cyhoeddwyd: The National Academy of Sciences 1999
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Biological Sciences
Mynediad Ar-lein:https://ncbi.nlm.nih.gov/pmc/articles/PMC17950/
https://ncbi.nlm.nih.gov/pubmed/10485893
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spelling pubmed-179502001-03-08 Muscle degeneration without mechanical injury in sarcoglycan deficiency Hack, A. A. Cordier, L. Shoturma, D. I. Lam, M. Y. Sweeney, H. L. McNally, E. M. Proc Natl Acad Sci U S A Biological Sciences In humans, mutations in the genes encoding components of the dystrophin–glycoprotein complex cause muscular dystrophy. Specifically, primary mutations in the genes encoding α-, β-, γ-, and δ-sarcoglycan have been identified in humans with limb-girdle muscular dystrophy. Mice lacking γ-sarcoglycan develop progressive muscular dystrophy similar to human muscular dystrophy. Without γ-sarcoglycan, β- and δ-sarcoglycan are unstable at the muscle membrane and α-sarcoglycan is severely reduced. The expression and localization of dystrophin, dystroglycan, and laminin-α2, a mechanical link between the actin cytoskeleton and the extracellular matrix, appears unaffected by the loss of sarcoglycan. We assessed the functional integrity of this mechanical link and found that isolated muscles lacking γ-sarcoglycan showed normal resistance to mechanical strain induced by eccentric muscle contraction. Sarcoglycan-deficient muscles also showed normal peak isometric and tetanic force generation. Furthermore, there was no evidence for contraction-induced injury in mice lacking γ-sarcoglycan that were subjected to an extended, rigorous exercise regimen. These data demonstrate that mechanical weakness and contraction-induced muscle injury are not required for muscle degeneration and the dystrophic process. Thus, a nonmechanical mechanism, perhaps involving some unknown signaling function, likely is responsible for muscular dystrophy where sarcoglycan is deficient. The National Academy of Sciences 1999-09-14 /pmc/articles/PMC17950/ /pubmed/10485893 Text en Copyright © 1999, The National Academy of Sciences
institution US National Library of Medicine
collection PubMed Central
language en
format Article
topic Biological Sciences
spellingShingle Biological Sciences
Hack, A. A.
Cordier, L.
Shoturma, D. I.
Lam, M. Y.
Sweeney, H. L.
McNally, E. M.
Muscle degeneration without mechanical injury in sarcoglycan deficiency
description In humans, mutations in the genes encoding components of the dystrophin–glycoprotein complex cause muscular dystrophy. Specifically, primary mutations in the genes encoding α-, β-, γ-, and δ-sarcoglycan have been identified in humans with limb-girdle muscular dystrophy. Mice lacking γ-sarcoglycan develop progressive muscular dystrophy similar to human muscular dystrophy. Without γ-sarcoglycan, β- and δ-sarcoglycan are unstable at the muscle membrane and α-sarcoglycan is severely reduced. The expression and localization of dystrophin, dystroglycan, and laminin-α2, a mechanical link between the actin cytoskeleton and the extracellular matrix, appears unaffected by the loss of sarcoglycan. We assessed the functional integrity of this mechanical link and found that isolated muscles lacking γ-sarcoglycan showed normal resistance to mechanical strain induced by eccentric muscle contraction. Sarcoglycan-deficient muscles also showed normal peak isometric and tetanic force generation. Furthermore, there was no evidence for contraction-induced injury in mice lacking γ-sarcoglycan that were subjected to an extended, rigorous exercise regimen. These data demonstrate that mechanical weakness and contraction-induced muscle injury are not required for muscle degeneration and the dystrophic process. Thus, a nonmechanical mechanism, perhaps involving some unknown signaling function, likely is responsible for muscular dystrophy where sarcoglycan is deficient.
author Hack, A. A.
Cordier, L.
Shoturma, D. I.
Lam, M. Y.
Sweeney, H. L.
McNally, E. M.
author_facet Hack, A. A.
Cordier, L.
Shoturma, D. I.
Lam, M. Y.
Sweeney, H. L.
McNally, E. M.
author_sort Hack, A. A.
title Muscle degeneration without mechanical injury in sarcoglycan deficiency
title_short Muscle degeneration without mechanical injury in sarcoglycan deficiency
title_full Muscle degeneration without mechanical injury in sarcoglycan deficiency
title_fullStr Muscle degeneration without mechanical injury in sarcoglycan deficiency
title_full_unstemmed Muscle degeneration without mechanical injury in sarcoglycan deficiency
title_sort muscle degeneration without mechanical injury in sarcoglycan deficiency
publisher The National Academy of Sciences
publisher_facet The National Academy of Sciences
publishDate 1999
url https://ncbi.nlm.nih.gov/pmc/articles/PMC17950/
https://ncbi.nlm.nih.gov/pubmed/10485893
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