A and B utrophin in human muscle and sarcolemmal A-utrophin associated with tumours.
Utrophin is an autosomal homologue of dystrophin, abnormal expression of which is responsible for X-linked Duchenne and Becker muscular dystrophy. In normal mature muscle utrophin is confined to blood vessels, nerves and myotendinous and neuromuscular junctions. When dystrophin is absent utrophin is abundant on the sarcolemma. This has raised the possibility that up-regulation of utrophin may be of therapeutic benefit. Two full-length transcripts of utrophin, A and B, have been identified, which are regulated by alternatively spliced 5' promoters. In dystrophic mouse muscle, the A isoform is present on the sarcolemma, whereas the B form is confined to blood vessels. We show here using immunohistochemistry and human isoform-specific antibodies that A- and B-utrophin localisation is the same in human muscle. The A isoform is present on the sarcolemma of foetal human muscle fibres, regenerating fibres, fibres deficient in dystrophin and on blood vessels and neuromuscular junctions. B-utrophin is only detected on blood vessels. We also show that muscle adjacent to some soft tissue tumours shows increased sarcolemmal utrophin-A, showing that utrophin and dystrophin can simultaneously localise to the sarcolemma and raising the possibility that factor(s) from the tumour cells or accompanying inflammatory cells may have a role in regulating utrophin.
Sewry
C A
CA
Department of Histopathology, Centre for Inherited Neuromuscular Disorders, Robert Jones and Agnes Hunt Orthopaedic and District Hospital, NHS Trust, Oswestry SY10 7AG, UK. c.sewry@imperial.ac.uk
Nowak
K J
KJ
Ehmsen
J T
JT
Davies
K E
KE
D000293:Adolescent; D016189:Dystrophin / Q000378:metabolism; D004622:Embryo, Mammalian; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007223:Infant; D036341:Intercellular Signaling Peptides and Proteins; D018482:Muscle, Skeletal / Q000378:metabolism*; D020388:Muscular Dystrophy, Duchenne / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism*; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D012508:Sarcolemma / Q000378:metabolism*; D049411:Utrophin / Q000145:classification / Q000378:metabolism*
D016189:Dystrophin; D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D011506:Proteins; C483599:UTRN protein, human; D049411:Utrophin; C095114:collapsin response mediator protein-2