Linked Life Data

20558759

Source:http://linkedlifedata.com/resource/pubmed/id/20558759

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2010-9-10
pubmed:abstractText
Mutations that result in the loss of the protein dysferlin result in defective muscle membrane repair and cause either a form of limb girdle muscular dystrophy (type 2B) or Miyoshi myopathy. Most patients are compound heterozygotes, often carrying one allele with a nonsense mutation. Using dysferlin-deficient mouse and human myocytes, we demonstrated that membrane blebbing in skeletal muscle myotubes in response to hypotonic shock requires dysferlin. Based on this, we developed an in vitro assay to assess rescue of dysferlin function in skeletal muscle myotubes. This blebbing assay may be useful for drug discovery/validation for dysferlin deficiency. With this assay, we demonstrate that the nonsense suppression drug, ataluren (PTC124), is able to induce read-through of the premature stop codon in a patient with a R1905X mutation in dysferlin and produce sufficient functional dysferlin (approximately 15% of normal levels) to rescue myotube membrane blebbing. Thus ataluren is a potential therapeutic for dysferlin-deficient patients harboring nonsense mutations.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1522-1601
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
109
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
901-5
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Membrane blebbing as an assessment of functional rescue of dysferlin-deficient human myotubes via nonsense suppression.
pubmed:affiliation
University of Pennsylvania School of Medicine, Department of Physiology, B400 Richards Bldg., 3700 Hamilton Walk, Philadelphia, PA 19104-6085, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural