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Loss of Dystrophin and β-Sarcoglycan, Respectively, Significantly Exacerbates the Phenotype of Laminin α2 Chain-Deficient Animals.

Gawlik, Kinga LU ; Holmberg, Johan K LU and Durbeej-Hjalt, Madeleine LU (2014) In American Journal of Pathology 184(3). p.740-752
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
American Journal of Pathology
volume
184
issue
3
pages
740 - 752
publisher
American Society for Investigative Pathology
external identifiers
  • pmid:24393714
  • wos:000332055500016
  • scopus:84894126274
ISSN
1525-2191
DOI
10.1016/j.ajpath.2013.11.017
language
English
LU publication?
yes
id
85d6dcce-89d3-4cf0-bd70-006517893de8 (old id 4291982)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/24393714?dopt=Abstract
date added to LUP
2014-02-06 21:28:37
date last changed
2017-10-01 03:04:29
@article{85d6dcce-89d3-4cf0-bd70-006517893de8,
  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.},
  author       = {Gawlik, Kinga and Holmberg, Johan K and Durbeej-Hjalt, Madeleine},
  issn         = {1525-2191},
  language     = {eng},
  number       = {3},
  pages        = {740--752},
  publisher    = {American Society for Investigative Pathology},
  series       = {American Journal of Pathology},
  title        = {Loss of Dystrophin and β-Sarcoglycan, Respectively, Significantly Exacerbates the Phenotype of Laminin α2 Chain-Deficient Animals.},
  url          = {http://dx.doi.org/10.1016/j.ajpath.2013.11.017},
  volume       = {184},
  year         = {2014},
}