Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P62988 (Ubiquitin)
 4,326 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Myofibrillar myopathy (MFM) is a group of disorders that are pathologically defined by the disorganization of the myofibrillar alignment associated with the intracellular accumulation of Z-disk-associated proteins. MFM is caused by mutations in genes encoding Z-disk-associated proteins, including myotilin. Although a number of MFM mutations have been identified, it has been difficult to elucidate the precise roles of the mutant proteins. Here, we present a useful method for the characterization of mutant proteins associated with MFM. Expression of mutant myotilins in mouse tibialis anterior muscle by in vivo electroporation recapitulated both the pathological changes and the biochemical characteristics observed in patients with myotilinopathy. In mutant myotilin-expressing muscle fibers, myotilin aggregates and is costained with polyubiquitin, and Z-disk-associated proteins and myofibrillar disorganization were commonly seen. In addition, the expressed S60C mutant myotilin protein displayed marked detergent insolubility in electroporated mouse muscle, similar to that observed in human MFM muscle with the same mutation. Thus, in vivo electroporation can be a useful method for evaluating the pathogenicity of mutations identified in MFM.
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PMID:In vivo characterization of mutant myotilins. 2234 1