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Am J Pathol. 2014 Mar;184(3):740-52. doi: 10.1016/j.ajpath.2013.11.017. Epub 2014 Jan 4.

Loss of dystrophin and β-sarcoglycan significantly exacerbates the phenotype of laminin α2 chain-deficient animals.

Author information

  • 1Muscle Biology Unit, Department of Experimental Medical Science, Lund University, Lund, Sweden.
  • 2Muscle Biology Unit, Department of Experimental Medical Science, Lund University, Lund, Sweden. Electronic address: madeleine.durbeej-hjalt@med.lu.se.

Abstract

The adhesion molecule laminin α2 chain interacts with the dystrophin-glycoprotein complex, contributes to normal muscle function, and protects skeletal muscles from damage. Complete loss of the laminin α2 chain in mice results in a severe muscular dystrophy phenotype and death at approximately 3 weeks of age. However, it is not clear if the remaining members of the dystrophin-glycoprotein complex further protect laminin α2 chain-deficient skeletal muscle fibers from degeneration. Hence, we generated mice deficient in laminin α2 chain and dystrophin (dy(3K)/mdx) and mice devoid of laminin α2 chain and β-sarcoglycan (dy(3K)/Sgcb). Severe muscular dystrophy and a lack of nourishment inevitably led to massive muscle wasting and death in double-knockout animals. The dy(3K)/Sgcb mice were generally more severely affected than dy(3K)/mdx mice. However, both double-knockout strains displayed exacerbated muscle degeneration, inflammation, fibrosis, and reduced life span (5 to 13 days) compared with single-knockout animals. However, neither extraocular nor cardiac muscle was affected in double-knockout animals. Our results suggest that, although laminin α2 chain, dystrophin, and β-sarcoglycan are all part of the same adhesion complex, they have complementary, but nonredundant, roles in maintaining sarcolemmal integrity and protecting skeletal muscle fibers from damage. Moreover, the double-knockout mice could potentially serve as models in which to study extremely aggressive muscle-wasting conditions.

Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

PMID:
24393714
[PubMed - in process]
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