Chimaeric mice deficient in dystroglycans develop muscular dystrophy and have disrupted myoneural synapses

  title={Chimaeric mice deficient in dystroglycans develop muscular dystrophy and have disrupted myoneural synapses},
  author={Patrice D. C{\^o}t{\'e} and Hakima Moukhles and Michael H. Lindenbaum and Salvatore Carbonetto},
  journal={Nature Genetics},
Mutations in the dystrophin gene (DMD) and in genes encoding several dystrophin-associated proteins result in Duchenne and other forms of muscular dystrophy. α-Dystroglycan (Dg) binds to laminins in the basement membrane surrounding each myofibre and docks with β-Dg, a transmembrane protein, which in turn interacts with dystrophin or utrophin in the subplasmalemmal cytoskeleton. α- and β-Dgs are thought to form the functional core of a larger complex of proteins extending from the basement… 

Genetic Engineering of Dystroglycan in Animal Models of Muscular Dystrophy

This review focuses specifically on the animal model systems that have been developed with the aim of directly engineering DAG1 in order to study the DG function in skeletal muscle as well as in other tissues.

Function and genetics of dystrophin and dystrophin-related proteins in muscle.

The role of the dystrophin complex and protein family in muscle is discussed and the physiological processes that are affected in Duchenne muscular dystrophy are described.

Dystroglycan contributes to the formation of multiple dystrophin‐like complexes in brain

In the brain, unlike in muscle, the association of syntrophin with dystrophin is not crucial for the DAP complex which suggests that it may be associated with other proteins.

Muscular dystrophy associated with α-dystroglycan deficiency in Sphynx and Devon Rex cats

Destabilization of the Dystrophin-Glycoprotein Complex without Functional Deficits in α-Dystrobrevin Null Muscle

It is shown that the biochemical association between dystrophin and β-dystroglycan is compromised in adbn−/− skeletal muscle, suggesting that α-dystrobrevin plays a structural role in stabilizing the DGC.

Role of dystrophin and utrophin for assembly and function of the dystrophin glycoprotein complex in non-muscle tissue

Focus on recent studies of the DGC in brain, blood-brain barrier and choroid plexus, retina, and kidney and discusses the role of dystrophin isoforms and utrophin for assembly of the complex in these tissues.

Overexpression of the cytotoxic T cell GalNAc transferase in skeletal muscle inhibits muscular dystrophy in mdx mice

It is shown that transgenic overexpression of the synaptic CT GalNAc transferase in the skeletal muscles of mdx animals (mdx/CT) increases the expression of utrophin and many DAPs, including dystroglyCans, sarcoglycans, and dystrobrevins, along myofibers, and should be considered as a target for therapeutic intervention in DMD.

Muscle-specific expression of LARGE restores neuromuscular transmission deficits in dystrophic LARGE(myd) mice.

It is demonstrated that, in addition to muscle degeneration and dystrophy, impaired neuromuscular transmission contributes to muscle weakness in dystrophic myd mice and that the noted defects are primarily due to the effects of LARGE and glycosylated dystroglycan in stabilizing the endplate of the NMJ.



Animal Models for Muscular Dystrophy Show Different Patterns of Sarcolemmal Disruption

The results suggest that the pathogenic mechanisms in congenital muscular dystrophy are different from those in Duchenne muscular Dystrophy, although the primary defects originate in two components associated with the same protein complex.

Forced expression of dystrophin deletion constructs reveals structure- function correlations

Data indicate that the cysteine-rich domain is critical for functional activity, presumably by mediating a direct interaction with beta-dystroglycan, however, the remainder of the COOH terminus is not required for assembly of the DAP complex.

Defective muscle basement membrane and lack of M-laminin in the dystrophic dy/dy mouse.

The dy mouse may provide a model for autosomal muscular dystrophies in humans and facilitate studies of functions of M-laminin, suggesting that a mutation in the M-chain gene causes the muscular dystrophy in dy/dy mice.

Co-localization and molecular association of dystrophin with laminin at the surface of mouse and human myotubes.

The results provide the first direct cellular evidence of a transmembrane linkage between dystrophin in the sarcolemmal cytoskeleton with laminIn in the overlying basal lamina.

Identification and Characterization of the Dystrophin Anchoring Site on β-Dystroglycan (*)

The identification of the interaction sites in dystrophin and β-dystroglycan provides further insight into the structure and the molecular organization of the dyStrophin-glycoprotein complex at the sarcolemma membrane and will be helpful for studying the pathogenesis of Duchenne muscular dystrophy.

α-Dystroglycan Is a Laminin Receptor Involved in Extracellular Matrix Assembly on Myotubes and Muscle Cell Viability

It is suggested that α-DG is a functional LN receptor in situ which is required for deposition of LN on the cell and, further, implicate α- DG in the maintenance of myotube viability.

Expression of Deletion-Containing Dystrophins in mdx Muscle: Implications for Gene Therapy and Dystrophin Function

Stabilization and co-localization of the DAP did seem to be a prerequisite for expression and/or stabilization of mutant dystrophins beyond 1 wk and these same criteria seemed important for mitigating the histopathological consequences of Dystrophin deficiency.

Dystroglycan is essential for early embryonic development: disruption of Reichert's membrane in Dag1-null mice.

The data indicate that dystroglycan is required for the development of Reichert's membrane, and suggests that disruption of basement membrane organization might be a common feature of muscular dystrophies linked to the DGC.

beta 2-Syntrophin: localization at the neuromuscular junction in skeletal muscle.

The syntrophins are a multigene family of proteins which bind C-terminal domains of dystrophin, utrophin and homologs thereof. We report here that antibodies specific for one isoform, beta