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Transgenic overexpression of laminin 1 chain in laminin 2 chain-deficient mice rescues the disease throughout the lifespan

Gawlik, Kinga LU and Durbeej-Hjalt, Madeleine LU (2010) In Muscle and Nerve 42(1). p.30-37
Abstract
Several approaches to treat laminin alpha 2 chain-deficient congenital muscular dystrophy (MDC1A) in mouse models have been undertaken. Most have shown promising results in young animals. However, older animals have only been characterized to some extent. Herein we analyze the lifespan of laminin alpha 2 chain deficient mice with transgenic overexpression of laminin alpha 1 chain. Further outcome measures included internalized myonuclei, heart fibrosis, grip strength, and serum creatine kinase activity. We show that laminin alpha 2-chain-deficient animals that overexpress laminin alpha 1 chain survive to up to 1.5-2 years of age. Furthermore, they displayed improved skeletal and heart muscle morphology, near-normal muscle strength, and... (More)
Several approaches to treat laminin alpha 2 chain-deficient congenital muscular dystrophy (MDC1A) in mouse models have been undertaken. Most have shown promising results in young animals. However, older animals have only been characterized to some extent. Herein we analyze the lifespan of laminin alpha 2 chain deficient mice with transgenic overexpression of laminin alpha 1 chain. Further outcome measures included internalized myonuclei, heart fibrosis, grip strength, and serum creatine kinase activity. We show that laminin alpha 2-chain-deficient animals that overexpress laminin alpha 1 chain survive to up to 1.5-2 years of age. Furthermore, they displayed improved skeletal and heart muscle morphology, near-normal muscle strength, and normalized creatine kinase levels. Such an improvement of the dystrophic phenotype that persists to old age has not been previously demonstrated in mice. Our findings hold promise with regard to the efficient treatment of MDC1A patients in the future. Muscle Nerve 42: 30-37, 2010 (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
muscular dystrophy, heart, gene therapy, muscle, laminin
in
Muscle and Nerve
volume
42
issue
1
pages
30 - 37
publisher
John Wiley & Sons
external identifiers
  • wos:000279456400005
  • scopus:77954104087
ISSN
0148-639X
DOI
10.1002/mus.21616
language
English
LU publication?
yes
id
6adaf207-c499-4774-a6d1-8a10b0b2cd14 (old id 1628963)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20544910?dopt=Abstract
date added to LUP
2010-07-23 11:19:35
date last changed
2018-06-03 03:08:21
@article{6adaf207-c499-4774-a6d1-8a10b0b2cd14,
  abstract     = {Several approaches to treat laminin alpha 2 chain-deficient congenital muscular dystrophy (MDC1A) in mouse models have been undertaken. Most have shown promising results in young animals. However, older animals have only been characterized to some extent. Herein we analyze the lifespan of laminin alpha 2 chain deficient mice with transgenic overexpression of laminin alpha 1 chain. Further outcome measures included internalized myonuclei, heart fibrosis, grip strength, and serum creatine kinase activity. We show that laminin alpha 2-chain-deficient animals that overexpress laminin alpha 1 chain survive to up to 1.5-2 years of age. Furthermore, they displayed improved skeletal and heart muscle morphology, near-normal muscle strength, and normalized creatine kinase levels. Such an improvement of the dystrophic phenotype that persists to old age has not been previously demonstrated in mice. Our findings hold promise with regard to the efficient treatment of MDC1A patients in the future. Muscle Nerve 42: 30-37, 2010},
  author       = {Gawlik, Kinga and Durbeej-Hjalt, Madeleine},
  issn         = {0148-639X},
  keyword      = {muscular dystrophy,heart,gene therapy,muscle,laminin},
  language     = {eng},
  number       = {1},
  pages        = {30--37},
  publisher    = {John Wiley & Sons},
  series       = {Muscle and Nerve},
  title        = {Transgenic overexpression of laminin 1 chain in laminin 2 chain-deficient mice rescues the disease throughout the lifespan},
  url          = {http://dx.doi.org/10.1002/mus.21616},
  volume       = {42},
  year         = {2010},
}