Transgenic overexpression of laminin alpha1 chain in laminin alpha2 chain-deficient mice rescues the disease throughout the lifespan.

Abstract:

:Several approaches to treat laminin alpha2 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 alpha2 chain-deficient mice with transgenic overexpression of laminin alpha1 chain. Further outcome measures included internalized myonuclei, heart fibrosis, grip strength, and serum creatine kinase activity. We show that laminin alpha2-chain-deficient animals that overexpress laminin alpha1 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.

journal_name

Muscle Nerve

journal_title

Muscle & nerve

authors

Gawlik KI,Durbeej M

doi

10.1002/mus.21616

subject

Has Abstract

pub_date

2010-07-01 00:00:00

pages

30-7

issue

1

eissn

0148-639X

issn

1097-4598

journal_volume

42

pub_type

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