Dystrobrevin deficiency at the sarcolemma of patients with muscular dystrophy.
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| Abstract |
Mutations in the genes encoding dystrophin or dystrophin-associated proteins are responsible for Duchenne muscular dystrophy or various forms of limb-girdle muscular dystrophies respectively. We have recently cloned the gene for the murine 87 kDa postsynaptic protein dystrobrevin, a dystrophin-associated protein. Anti-dystrobrevin antibodies stain the sarcolemma in normal skeletal muscle indicating that dystrobrevin co-localises with dystrophin and the dystrophin-associated protein complex. By contrast, dystrobrevin membrane staining is severely reduced in muscles of Duchenne muscular dystrophy patients, consistent with dystrobrevin being a dystrophin-associated protein. Interestingly, dystrobrevin staining at the sarcolemma is dramatically reduced in patients with limb-girdle muscular dystrophy arising from the loss of one or all of the sarcoglycan components. Normal dystrobrevin staining is observed in patients with other forms of limb-girdle muscular dystrophy where dystrophin and the rest of the dystrophin-associated protein complex are normally expressed and in other neuromuscular disorders. Our results show that dystrobrevin-deficiency is a generic feature of dystrophies linked to dystrophin and the dystrophin-associated proteins. This is the first indication that a cytoplasmic component of the dystrophin-associated protein complex may be involved in the pathogenesis of limb-girdle muscular dystrophy.
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| Authors | L Metzinger, D J Blake, M V Squier, L V Anderson, A E Deconinck, R Nawrotzki, D Hilton-Jones, K E Davies |
| Journal | Human molecular genetics (Hum Mol Genet) Vol. 6 Issue 7 Pg. 1185-91 (Jul 1997) ISSN: 0964-6906 [Print] England |
| PMID | 9215691 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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