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Laminin α1 reduces muscular dystrophy in dy2Jmice

Gawlik, Kinga I. LU ; Harandi, Vahid M. LU ; Cheong, Rachel Y. LU ; Petersén, Åsa LU and Durbeej, Madeleine LU (2018) In Matrix Biology
Abstract

Muscular dystrophies, including laminin α2 chain-deficient muscular dystrophy (LAMA2-CMD), are associated with immense personal, social and economic burdens. Thus, effective treatments are urgently needed. LAMA2-CMD is either a severe, early-onset condition with complete laminin α2 chain-deficiency or a milder, late-onset form with partial laminin α2 chain-deficiency. Mouse models dy 3K /dy 3K and dy 2J /dy 2J , respectively, recapitulate these two forms of LAMA2-CMD very well. We have previously demonstrated that laminin α1 chain significantly reduces muscular dystrophy in laminin α2 chain-deficient dy 3K /dy 3K mice. Among all the different pre-clinical... (More)

Muscular dystrophies, including laminin α2 chain-deficient muscular dystrophy (LAMA2-CMD), are associated with immense personal, social and economic burdens. Thus, effective treatments are urgently needed. LAMA2-CMD is either a severe, early-onset condition with complete laminin α2 chain-deficiency or a milder, late-onset form with partial laminin α2 chain-deficiency. Mouse models dy 3K /dy 3K and dy 2J /dy 2J , respectively, recapitulate these two forms of LAMA2-CMD very well. We have previously demonstrated that laminin α1 chain significantly reduces muscular dystrophy in laminin α2 chain-deficient dy 3K /dy 3K mice. Among all the different pre-clinical approaches that have been evaluated in mice, laminin α1 chain-mediated therapy has been shown to be one of the most effective lines of attack. However, it has remained unclear if laminin α1 chain-mediated treatment is also applicable for partial laminin α2 chain-deficiency. Hence, we have generated dy 2J /dy 2J mice (that express a substantial amount of an N-terminal truncated laminin α2 chain) overexpressing laminin α1 chain in the neuromuscular system. The laminin α1 chain transgene ameliorated the dystrophic phenotype, restored muscle strength and reduced peripheral neuropathy. Thus, these findings provide additional support for the development of laminin α1 chain-based therapy for LAMA2-CMD.

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author
organization
publishing date
type
Contribution to journal
publication status
epub
subject
keywords
Basement membrane, Laminin, Muscular dystrophy, Therapy
in
Matrix Biology
publisher
Elsevier
external identifiers
  • scopus:85043363212
ISSN
0945-053X
language
English
LU publication?
yes
id
1e8d1b89-caaf-43b1-8612-ac02468a5c8f
date added to LUP
2018-03-22 13:11:06
date last changed
2019-03-19 03:51:31
@article{1e8d1b89-caaf-43b1-8612-ac02468a5c8f,
  abstract     = {<p>Muscular dystrophies, including laminin α2 chain-deficient muscular dystrophy (LAMA2-CMD), are associated with immense personal, social and economic burdens. Thus, effective treatments are urgently needed. LAMA2-CMD is either a severe, early-onset condition with complete laminin α2 chain-deficiency or a milder, late-onset form with partial laminin α2 chain-deficiency. Mouse models dy <sup> 3K </sup> /dy <sup> 3K </sup> and dy <sup> 2J </sup> /dy <sup> 2J </sup>, respectively, recapitulate these two forms of LAMA2-CMD very well. We have previously demonstrated that laminin α1 chain significantly reduces muscular dystrophy in laminin α2 chain-deficient dy <sup> 3K </sup> /dy <sup> 3K </sup> mice. Among all the different pre-clinical approaches that have been evaluated in mice, laminin α1 chain-mediated therapy has been shown to be one of the most effective lines of attack. However, it has remained unclear if laminin α1 chain-mediated treatment is also applicable for partial laminin α2 chain-deficiency. Hence, we have generated dy <sup> 2J </sup> /dy <sup> 2J </sup> mice (that express a substantial amount of an N-terminal truncated laminin α2 chain) overexpressing laminin α1 chain in the neuromuscular system. The laminin α1 chain transgene ameliorated the dystrophic phenotype, restored muscle strength and reduced peripheral neuropathy. Thus, these findings provide additional support for the development of laminin α1 chain-based therapy for LAMA2-CMD.</p>},
  author       = {Gawlik, Kinga I. and Harandi, Vahid M. and Cheong, Rachel Y. and Petersén, Åsa and Durbeej, Madeleine},
  issn         = {0945-053X},
  keyword      = {Basement membrane,Laminin,Muscular dystrophy,Therapy},
  language     = {eng},
  month        = {03},
  publisher    = {Elsevier},
  series       = {Matrix Biology},
  title        = {Laminin α1 reduces muscular dystrophy in dy<sup>2J</sup>mice},
  year         = {2018},
}