INTRODUCTION Congenital muscular dystrophy is a distinct group of diseases presenting with weakness in infancy or childhood and no current therapy. One form, MDC1A, is the result of laminin alpha-2 deficiency and results in significant weakness, respiratory insufficiency and early death. Modification of apoptosis is one potential pathway for therapy in these patients. METHODS dy(2J) mice were...

Laminin alpha2-deficient congenital muscular dystrophy, called MDC1A, is a rare, devastating genetic disease characterized by severe neonatal hypotonia ("floppy infant syndrome"), peripheral neuropathy, inability to stand or walk, respiratory distress, and premature death in early life. Transgenic overexpression of the apoptosis inhibitor protein BCL-2, or deletion of the proapoptotic Bax gene ...

Mutations in LAMA2 cause a severe form of congenital muscular dystrophy, called MDC1A. Studies in mouse models have shown that transgenic expression of a designed, miniaturized form of the extracellular matrix molecule agrin ('mini-agrin') or apoptosis inhibition by either overexpression of Bcl2 or application of the pharmacological substance omigapil can ameliorate the disease. Here, we tested...

Laminin trimers composed of a , b , and g chains are major components of basal laminae (BLs) throughout the body. To date, three a chains ( a 1–3) have been shown to assemble into at least seven heterotrimers (called laminins 1–7). Genes encoding two additional a chains ( a 4 and a 5) have been cloned, but little is known about their expression, and their protein products have not been identifi...

muscle biopsy interpretation has been revolutionized by ihc. immunohistochemistry now has an essential role in the evaluation of the muscle biopsies and in examining proteins localizations. advances in the characterization of sarcolemmal proteins and recognition that defects in the genes encoding such proteins may lie at the heart of the multiple differing forms of muscular dystrophy have been ...

BACKGROUND Laminin alpha2 chain mutations cause congenital muscular dystrophy with dysmyelination neuropathy (MDC1A). Previously, we demonstrated that laminin alpha1 chain ameliorates the disease in mice. Dystroglycan and integrins are major laminin receptors. Unlike laminin alpha2 chain, alpha1 chain binds the receptors by separate domains; laminin globular (LG) domains 4 and LG1-3, respective...

Dr. Girgenrath discussed her data on MDC1A, which is a severe form of congenital muscular dystrophy characterized by hypotonia, muscle weakness, and premature death. MDC1A results from deficiency in the laminin alpha 2 chain of laminin-211, an extracellular matrix protein mainly found in skeletal muscle and Schwann cells. Defects in laminin-211 cause major disruption of structural stability and...

Unlike the cells of many tissues, muscle and neuronal cells do not replicate throughout life. Therefore there has to be an eVective mechanism of inducing local repair and preventing cell death. We have identified and cloned two growth factors that are expressed by muscle when it is subjected to activity which are derived from the insulin like growth factor-I (IGF-I) gene by alternative splicing...

IT IS GENERALLY AGREED that successful skeletal muscle regeneration following intense exercise or injury is facilitated by the protein synthesis machinery and the recruitment of myogenic stem (satellite) cells. Upstream activation of these processes, however, is poorly understood. A growing body of evidence suggests cyclooxygenase (COX) activity plays an important role, as COX inhibition via no...

Unlike the cells of many tissues, muscle and neuronal cells do not replicate throughout life. Therefore there has to be an eVective mechanism of inducing local repair and preventing cell death. We have identified and cloned two growth factors that are expressed by muscle when it is subjected to activity which are derived from the insulin like growth factor-I (IGF-I) gene by alternative splicing...