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Laminin {alpha}1 chain reduces muscular dystrophy in laminin {alpha}2 chain deficient mice.

Gawlik, Kinga LU ; Miyagoe-Suzuki, Yuko; Ekblom, Peter LU ; Takeda, Shin'ichi and Durbeej-Hjalt, Madeleine LU (2004) In Human Molecular Genetics 13(16). p.1775-1784
Abstract
Laminin (LN) {alpha}2 chain deficiency in humans and mice leads to severe forms of congenital muscular dystrophy (CMD). Here, we investigated whether LN{alpha}1 chain in mice can compensate for the absence of LN{alpha}2 chain and prevent the development of muscular dystrophy. We generated mice expressing a LN{alpha}1 chain transgene in skeletal muscle of LN{alpha}2 chain deficient mice. LN{alpha}1 is not normally expressed in muscle, but the transgenically produced LN{alpha}1 chain was incorporated into muscle basement membranes, and normalized the compensatory changes of expression of certain other laminin chains ({alpha}4, ß2). In 4-month-old mice, LN{alpha}1 chain could fully prevent the development of muscular dystrophy in several... (More)
Laminin (LN) {alpha}2 chain deficiency in humans and mice leads to severe forms of congenital muscular dystrophy (CMD). Here, we investigated whether LN{alpha}1 chain in mice can compensate for the absence of LN{alpha}2 chain and prevent the development of muscular dystrophy. We generated mice expressing a LN{alpha}1 chain transgene in skeletal muscle of LN{alpha}2 chain deficient mice. LN{alpha}1 is not normally expressed in muscle, but the transgenically produced LN{alpha}1 chain was incorporated into muscle basement membranes, and normalized the compensatory changes of expression of certain other laminin chains ({alpha}4, ß2). In 4-month-old mice, LN{alpha}1 chain could fully prevent the development of muscular dystrophy in several muscles, and partially in others. The LN{alpha}1 chain transgene not only reversed the appearance of histopathological features of the disease to a remarkable degree, but also greatly improved health and longevity of the mice. Correction of LN{alpha}2 chain deficiency by LN{alpha}1 chain may serve as a paradigm for gene therapy of CMD in patients. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Human Molecular Genetics
volume
13
issue
16
pages
1775 - 1784
publisher
Oxford University Press
external identifiers
  • wos:000222880700009
  • pmid:15213105
  • scopus:4444354572
ISSN
0964-6906
DOI
10.1093/hmg/ddh190
language
English
LU publication?
yes
id
c435c8d8-014f-4035-b2f6-15f78c35ff86 (old id 123960)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15213105&dopt=Abstract
date added to LUP
2007-07-12 13:00:33
date last changed
2017-09-03 03:48:20
@article{c435c8d8-014f-4035-b2f6-15f78c35ff86,
  abstract     = {Laminin (LN) {alpha}2 chain deficiency in humans and mice leads to severe forms of congenital muscular dystrophy (CMD). Here, we investigated whether LN{alpha}1 chain in mice can compensate for the absence of LN{alpha}2 chain and prevent the development of muscular dystrophy. We generated mice expressing a LN{alpha}1 chain transgene in skeletal muscle of LN{alpha}2 chain deficient mice. LN{alpha}1 is not normally expressed in muscle, but the transgenically produced LN{alpha}1 chain was incorporated into muscle basement membranes, and normalized the compensatory changes of expression of certain other laminin chains ({alpha}4, ß2). In 4-month-old mice, LN{alpha}1 chain could fully prevent the development of muscular dystrophy in several muscles, and partially in others. The LN{alpha}1 chain transgene not only reversed the appearance of histopathological features of the disease to a remarkable degree, but also greatly improved health and longevity of the mice. Correction of LN{alpha}2 chain deficiency by LN{alpha}1 chain may serve as a paradigm for gene therapy of CMD in patients.},
  author       = {Gawlik, Kinga and Miyagoe-Suzuki, Yuko and Ekblom, Peter and Takeda, Shin'ichi and Durbeej-Hjalt, Madeleine},
  issn         = {0964-6906},
  language     = {eng},
  number       = {16},
  pages        = {1775--1784},
  publisher    = {Oxford University Press},
  series       = {Human Molecular Genetics},
  title        = {Laminin {alpha}1 chain reduces muscular dystrophy in laminin {alpha}2 chain deficient mice.},
  url          = {http://dx.doi.org/10.1093/hmg/ddh190},
  volume       = {13},
  year         = {2004},
}