The structural and functional diversity of dystrophin

  title={The structural and functional diversity of dystrophin},
  author={Andrew H. Ahn and Louis M. Kunkel},
  journal={Nature Genetics},
Duchenne and Becker muscular dystrophies are caused by defects of the dystrophin gene. Expression of this large X-linked gene is under elaborate transcriptional and splicing control. At least five independent promoters specify the transcription of their respective alternative first exons in a cell-specific and developmentally controlled manner. Three promoters express full-length dystrophin, while two promoters near the C terminus express the last domains in a mutually exclusive manner. Six… 

The emerging family of dystrophin-related proteins.

Prevention of dystrophic pathology in mdx mice by a truncated dystrophin isoform.

Results indicate that viral delivery of dystrophin to a simple majority of fibers in a muscle group would greatly reduce the dystrophic pathology associated with Duchenne muscular dystrophy.

Altered mRNA splicing of dystrophin in type 1 myotonic dystrophy

It is suggested that the aberrantly spliced dystrophin is responsible for the muscle wasting in DM1.

Redirecting splicing to address dystrophin mutations: molecular by-pass surgery.

From interesting in vitro experiments several years ago, the dystrophin exon-skipping field has progressed to the stage of planning for clinical trials, which may be regarded as a form of by-pass surgery at the molecular level.

Antisense-induced exon skipping and synthesis of dystrophin in the mdx mouse.

This approach should reduce the severity of DMD by allowing a dystrophic gene transcript to be modified, such that it can be translated into a Becker-dystrophin-like protein.

Dystrophin and utrophin: Genetic analyses of their role in skeletal muscle

These animal models have led to a delineation of protein functions and localization patterns that will be useful for the generation of potential therapies for DMD, and are presented in the context of other known interactions at the muscle membrane.

Molecular Genetics of Dystrophinopathies

The commonest mutational event in the dystrophin gene is represented by intragenic deletions accounting for 65% of dyStrophin mutations, and frame-shift mutations are related to the absence of protein production and a DMD phenotype.



Tissue distribution of the dystrophin-related gene product and expression in the mdx and dy mouse.

  • D. LoveG. Morris K. Davies
  • Biology, Medicine
    Proceedings of the National Academy of Sciences of the United States of America
  • 1991
It is shown that a dystrophin-related locus (DMDL for Duchenne muscular dystrophy-like) on human chromosome 6 that maps close to the dy mutation on mouse chromosome 10 is expressed in a wide range of tissues at varying levels.

An alternative dystrophin transcript specific to peripheral nerve

A 5.2 kilobase transcript is described, expressed specifically in peripheral nerve, that initiates at a previously unrecognized exon located ∼850 basepairs upstream of dystrophin exon 56, arguing that it functions differently in the Schwann cell than does the major dystophin transcript in muscle.

Enormous dystrophin in a patient with Becker muscular dystrophy

This observation is of significant biologic interest in that, despite the gross alteration of the gene and the encoded protein, the patient has a relatively mild clinical progression compatible with a diagnosis of Becker muscular dystrophy.

Deficiency of a glycoprotein component of the dystrophin complex in dystrophic muscle

It is shown that four glycoproteins are integral components of the dystrophin complex and that the concentration of one of these is greatly reduced in DMD patients, suggesting the reduction in this glycoprotein may be one of the first stages of the molecular pathogenesis of muscular dystrophy.

An autosomal transcript in skeletal muscle with homology to dystrophin

THE Duchenne muscular dystrophy (DMD) gene has been localized to chromosome Xp211–6 and codes for a 14-kilobase (kb) transcript7 and a protein called dystrophin8, of relative molecular mass 427,000.

Alternative splicing of human dystrophin mRNA generates isoforms at the carboxy terminus

It is found that the first exon of the human dystrophin transcript is different in brain and muscle, indicating that dyStrophin expression could be differentially regulated in these tissues by usage of distinct promoters.

Dystrophin is transcribed in brain from a distant upstream promoter.

It is predicted that specific loss of the brain promoter may be one cause of X chromosome-linked mental retardation in patients with Duchenne muscular dystrophy.

Primary structure of dystrophin-related protein

To investigate the relationship between DRP and dystrophin in more detail, the whole DRP cDNA is cloned and sequenced and it is suggested that they derive from a common ancestral gene.