Expression profiling in exercised mdx suggests a role for extracellular proteins in the dystrophic muscle immune response.

Duchenne muscular dystrophy (DMD) is a lethal muscle wasting disorder caused by mutations in the DMD gene that leads to the absence or severe reduction of dystrophin protein in muscle. The mdx mouse, also dystrophin deficient, is the model most widely used to study the pathology and test potential therapies, but the phenotype is milder than human DMD. This limits the magnitude and range of histological damage parameters and molecular changes that can be measured in pre-clinical drug testing.

Altered mitogen-activated protein kinase signaling in dystrophic (mdx) muscle.

Introduction: Duchenne muscular dystrophy (DMD) results from a deficiency in the protein, dystrophin. Dystrophic myotubes are susceptible to stressful stimuli. This may be partly due to altered regulation of pro-survival signaling pathways, but a role for mitogen-activated protein (MAP) kinases has not been investigated.

Alterations in the expression of leukemia inhibitory factor following exercise: comparisons between wild-type and mdx muscles.

Background: Leukemia inhibitory factor (LIF) is a pleiotropic cytokine, belonging to the interleukin-6 family of cytokines, that has been suggested to have positive effects on myogenesis following injury and to minimise dystrophic pathology in mdx mice. Previous reports have suggested that Lif mRNA is up-regulated in the limb and diaphragm muscles of mdx mice, in human cases of dystrophy and acutely following exercise. This study examined expression of Lif mRNA in the quadriceps muscles of mdx and wild-type mice that were either sedentary or allowed to exercise voluntarily for two weeks.

Voluntary wheel running in dystrophin-deficient (mdx) mice: Relationships between exercise parameters and exacerbation of the dystrophic phenotype.

Voluntary wheel running can potentially be used to exacerbate the disease phenotype in dystrophin-deficient mdx mice. While it has been established that voluntary wheel running is highly variable between individuals, the key parameters of wheel running that impact the most on muscle pathology have not been examined in detail. We conducted a 2-week test of voluntary wheel running by mdx mice and the impact of wheel running on disease pathology.

Dystrophic pathology in the intrinsic and extrinsic laryngeal muscles in the mdx mouse.

Objective: This study aimed to characterize the laryngeal muscles in the mdx mouse model of Duchenne muscular dystrophy (DMD).

Design: Pathology was analyzed in the intrinsic and extrinsic laryngeal muscles from mdx mice and compared with other mdx muscle groups and with muscles from age-matched normal control mice.

Setting: In DMD, a dystrophin protein deficiency causes skeletal muscle breakdown.

Altered caveolin-3 expression disrupts PI(3) kinase signaling leading to death of cultured muscle cells.

Caveolae and their coat proteins, caveolins, co-ordinate multiple signaling pathways. Caveolin-3 is a muscle-specific caveolin isoform that is deficient in limb girdle muscular dystrophy type 1 C (LGMD1C). Paradoxically, overexpression of this protein also causes muscle degeneration in vivo.

Notch-mediated restoration of regenerative potential to aged muscle.

A hallmark of aging is diminished regenerative potential of tissues, but the mechanism of this decline is unknown. Analysis of injured muscle revealed that, with age, resident precursor cells (satellite cells) had a markedly impaired propensity to proliferate and to produce myoblasts necessary for muscle regeneration. This was due to insufficient up-regulation of the Notch ligand Delta and, thus, diminished activation of Notch in aged, regenerating muscle.

A caveolin-3 mutant that causes limb girdle muscular dystrophy type 1C disrupts Src localization and activity and induces apoptosis in skeletal myotubes.

Caveolins are membrane proteins that are the major coat proteins of caveolae, specialized lipid rafts in the plasma membrane that serve as scaffolding sites for many signaling complexes. Among the many signaling molecules associated with caveolins are the Src tyrosine kinases, whose activation regulates numerous cellular functions including the balance between cell survival and cell death. Several mutations in the muscle-specific caveolin, caveolin-3, lead to a form of autosomal dominant muscular dystrophy referred to as limb girdle muscular dystrophy type 1C (LGMD-1C).

Adeno-associated virus-mediated vascular endothelial growth factor gene therapy in skeletal muscle before transplantation promotes revascularization of regenerating muscle.

Successful clinical transplantation of whole skeletal muscles can be limited by impaired muscle revascularization and regeneration. The aim of this study was to enhance the revascularization (and hence speed of regeneration) of transplanted whole muscles by transducing muscles with the vascular endothelial growth factor (VEGF) gene before transplantation, using a recombinant adeno-associated virus (rAAV). The rAAV encoding VEGF and green fluorescent protein (GFP) (rAAV.