Isolation of candidate cDNAs for portions of the Duchenne muscular dystrophy gene

Abstract

Duchenne muscular dystrophy (DMD) and the less severe Becker muscular dystrophy (BMD) are human X-linked muscle-wasting disorders that have been localized to the band Xp21 by genetic linkage analysis and cytologically detectable abnormalities. A cloned DNA segment, DXS164 (or pERT87), has been shown to detect deletions in the DNA of unrelated DMD and BMD males. Here we present the nucleotide sequence of two highly conserved DNA fragments from the DXS164 locus and their homologous sequences from the mouse X chromosome. One of the human conserved segments hybridized to a large transcript in RNA isolated from human fetal skeletal muscle and was used to isolate cDNA clones which cover approximately 10% of this transcript. The cDNA clones map to Xp21 and hybridize with a minimum of eight small regions that span 130 kilobases (kb) of the DXS164 locus. These expressed sequences are candidates for portions of the gene responsible for both DMD and BMD.

Bex1 knock out mice show altered skeletal muscle regeneration

“…When this controlled repair system is impaired, continuous muscle degeneration and regeneration can occur [3]. Such is the case with Duchenne's muscular dystrophy (DMD), the most common form of inherited neuromuscular disorder [4]. The absence of dystrophin, a membrane-associated protein, is clearly the underlying cause [5].…”

“…Experiments performed using cDNA-based microarrays have identified highly coordinated molecular changes involved in skeletal muscle regeneration following cardiotoxin (CTX)-induced injury, a reproducible method to induce muscle regeneration [9,10]. Mdx mice [6] possess a mutation in the gene coding dystrophin, the protein that is absent in humans with DMD [4]. Histological findings, such as centrally nucleated fibers, inflammation, and heterogeneity of fiber size, are similar in the skeletal muscle of mdx mice and of patients with DMD [11].…”

Noninvasive monitoring of therapeutic gene transfer in animal models of muscular dystrophies

“…1 For example, dystrophin, a 427 kDa protein which links the F-actin to transmembrane components of the DGC, is mutated in the X-linked Duchenne muscular dystrophy (DMD) and in the milder Becker muscular dystrophy (BMD), while the transmembrane glycoproteins, a-, b-, g-and dsarcoglycans, are mutated in several recessive forms of limb-girdle muscular dystrophies (LGMD2D, E, C and F, respectively). [2][3][4][5][6][7][8] These disorders are characterized clinically by an increase in serum creatine kinase level and an involvement of specific groups of muscles, especially those of proximal part of the limbs, that is often associated with pseudo-hypertrophy of the calves. The dystrophic features in muscle biopsies present as fibers with central nucleation reflecting regeneration, inflammatory infiltrates, fiber splitting, fibrosis and necrosis.…”

MicroRNA-199a is induced in dystrophic muscle and affects WNT signaling, cell proliferation, and myogenic differentiation

“…Duchenne muscular dystrophy (DMD) is caused by mutations in the X-linked dystrophin gene. 1 Although the molecular cause of the disease is well documented, the secondary signaling pathways that are altered by the lack of a functional dystrophin protein remain understudied. 2,3 Dystrophic muscle is known to undergo cycles of regeneration to form new myofibers as a consequence of myofibers loss and myoblast cell dysregulation.…”