Laminin {alpha}1 chain reduces muscular dystrophy in laminin {alpha}2 chain deficient mice.
Författare
Summary, in English
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.
Publiceringsår
2004
Språk
Engelska
Sidor
1775-1784
Publikation/Tidskrift/Serie
Human Molecular Genetics
Volym
13
Issue
16
Länkar
Dokumenttyp
Artikel i tidskrift
Förlag
Oxford University Press
Ämne
- Medical Genetics
Status
Published
Forskningsgrupp
- Muscle Biology
ISBN/ISSN/Övrigt
- ISSN: 0964-6906