Cell and fiber type distribution of dystrophin

Molecular and functional analysis of the muscle-specific promoter region of the Duchenne muscular dystrophy gene.

“…The low but significant levels of dystrophin mRNA in kidney tissue is surprising and merits further investigation. In this regard, Hoffman et al (30) have suggested that the presence of significant levels of dystrophin in nonmuscle tissues (excluding the brain) can be attributed to the contribution from vascular smooth muscle within these tissues.…”

“…DMD cDNA-derived fusion protein-and synthetic peptide-generated antibodies have identified the DMD gene product as a 400-kilodalton protein (dystrophin) that is localized primarily to the sarcolemma of skeletal muscle fibers (2,5,69,72). Western blot (immunoblot) analysis has indicated that dystrophin is found in adult and fetal skeletal and cardiac muscle, the smooth muscle of the gastrointestinal and vascular systems, and in the brain cortex (30,31). The identification of regions within dystrophin that are homologous to the actin-binding domain of alpha-actinin (29) and the spectrin repeat unit (19), along with its apparent association with one or more integral sarcolemmal glycoproteins (12), suggests that dystrophin is a cytoskeletal protein involved in the management of contraction-induced stress.…”

Dystrophin is transcribed in brain from a distant upstream promoter.

“…Dystrophin, a large (427 kDa) protein with amino acid sequence homology to the spectrin family of membrane cytoskeletal proteins (2)(3)(4), is most abundant in skeletal and cardiac muscle, where it has been localized to the inner face of the plasma membrane (5)(6)(7)(8). Dystrophin is also found throughout the body in smooth muscle (9). DMD results from severely reduced amounts of dystrophin, whereas the milder Becker muscular dystrophy results primarily from mutations that generate dystrophin of abnormal molecular weight or quantity (10,11).…”

“…It is hypothesized that dystrophin might serve to stabilize the plasma membrane during muscle fiber contraction and that absence of dystrophin leads to membrane disruption and muscle fiber necrosis (6,12). The only nonmuscle tissue that expresses significant levels of dystrophin is the brain (1,9,13,14).…”

“…The presence ofdystrophin in the brain has revived interest in the possible central (1,9,13,14), making analysis of dystrophin in the brain difficult. Nevertheless, it is known that dystrophin mRNA in the brain contains different sequences at the 5' terminus from that found in muscle, suggesting that dystrophin is transcribed from an alternate promoter or is alternatively spliced in the brain (16,17).…”