An autosomal transcript in skeletal muscle with homology to dystrophin

Abstract

The Duchenne muscular dystrophy (DMD) gene has been localized to chromosome Xp21 and codes for a 14-kilobase (kb) transcript and a protein called dystrophin, of relative molecular mass 427,000. Dystrophin is associated with the cytoplasmic face of muscle fibre membranes and its C-terminal domain is thought to mediate membrane attachment. Although N-terminal and central domain structures share common features with other cytoskeletal components, no significant sequence similarity between the C-terminal region of dystrophin and other previously characterized proteins has been described. Here we report that fragments from the C-terminal domain of the DMD complementary DNA detect a closely related sequence which exhibits nucleic-acid and predicted amino-acid identities with dystrophin of approximately 65 and 80%, respectively. The dystrophin-related sequence identifies a 13-kb transcript in human fetal muscle and maps to chromosome 6. Thus, dystrophin may be a member of a family of functionally related large structural proteins in muscle.

Expression of the dystrophin‐related protein (utrophin) gene during mouse embryogenesis

“…Preliminary studies suggest that the UTRN gene has a similar, if not identical, multi-exon, structure to the DMD gene (Love et al, 1989) (unpublished data). It is not clear whether UTRN will be equally susceptible to deletions leading to protein deficiency and a t present no human disease has been associated with abnormalities a t the UTRN locus.…”

“…The dystrophin related protein gene (the name utrophin [UTRN] was recently approved by Genome Data Base-formerly referred to as Duchenne muscular dystrophy-like [DMDL] or DRP) is an autosomal homologue of the X-linked Duchenne muscular dystrophy (DMD) gene and is localised on human chromosome 6q24 and mouse chromosome 10 (Love et al, 1989;Buckle et al, 1990;Khurana et al, 1990). The UTRN transcript is large, 13kb, and codes for a 395 kDa protein thi Man Nguyen et al, 1991; 0 1993 WILEY-LISS.…”

Prevention of the dystrophic phenotype in dystrophin/utrophin-deficient muscle following adenovirus-mediated transfer of a utrophin minigene

“…8 Utrophin is a ubiquitously expressed protein similar in amino acid sequence to dystrophin. 9,10 In adult skeletal muscle, however, it is restricted to the neuromuscular and myotendinous junctions and is thought to play a role in the maintenance of junctional folds. 11 Studies in vitro have shown that utrophin is able to bind both to actin and to the DPC.…”

Expression of utrophin and its mRNA in denervated mdx mouse muscle

“…Further studies revealed that this gene encodes a large cytoskeletal protein highly homologous to dystrophin in its C-terminus [8] and that it presents a genomic organization similar to the structure of the dystrophin gene [9,10]. The utrophin gene is located on chromosome 6 in human and 10 in mouse [4,11].…”

“…[2,3]). In 1989, Love et al [4] showed the existence of an autosomal homologue to dystrophin subsequently named utrophin since it is expressed in a variety of tissues ( [5,6], and see for review [7]). Further studies revealed that this gene encodes a large cytoskeletal protein highly homologous to dystrophin in its C-terminus [8] and that it presents a genomic organization similar to the structure of the dystrophin gene [9,10].…”