Linked Life Data

15254015

Source:http://linkedlifedata.com/resource/pubmed/id/15254015

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
18
pubmed:dateCreated
2004-8-26
pubmed:abstractText
Limb girdle muscular dystrophy type 2B and Miyoshi myopathy are clinically distinct forms of muscular dystrophy that arise from defects in the dysferlin gene. Here, we report two novel lines of dysferlin-deficient mice obtained by (a) gene targeting and (b) identification of an inbred strain, A/J, bearing a retrotransposon insertion in the dysferlin gene. The mutations in these mice were located at the 3' and 5' ends of the dysferlin gene. Both lines of mice lacked dysferlin and developed a progressive muscular dystrophy with histopathological and ultrastructural features that closely resemble the human disease. Vital staining with Evans blue dye revealed loss of sarcolemmal integrity in both lines of mice, similar to that seen in mdx and caveolin-3 deficient mice. However, in contrast to the latter group of animals, the dysferlin-deficient mice have an intact dystrophin glycoprotein complex and normal levels of caveolin-3. Our findings indicate that muscle membrane disruption and myofiber degeneration in dysferlinopathy were directly mediated by the loss of dysferlin via a new pathogenic mechanism in muscular dystrophies. We also show that the mutation in the A/J mice arose between the late 1970s and the early 1980s, and had become fixed in the production breeding stocks. Therefore, all studies involving the A/J mice or mice derived from A/J, including recombinant inbred, recombinant congenic and chromosome substitution strains, should take into account the dysferlin defect in these strains. These new dysferlin-deficient mice should be useful for elucidating the pathogenic pathway in dysferlinopathy and for developing therapeutic strategies.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0964-6906
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
13
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1999-2010
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:15254015-Animals, pubmed-meshheading:15254015-Calpain, pubmed-meshheading:15254015-Caveolin 3, pubmed-meshheading:15254015-Caveolins, pubmed-meshheading:15254015-Disease Models, Animal, pubmed-meshheading:15254015-Dystrophin, pubmed-meshheading:15254015-Gene Expression, pubmed-meshheading:15254015-Gene Targeting, pubmed-meshheading:15254015-Humans, pubmed-meshheading:15254015-Membrane Proteins, pubmed-meshheading:15254015-Mice, pubmed-meshheading:15254015-Mice, Mutant Strains, pubmed-meshheading:15254015-Muscle, Skeletal, pubmed-meshheading:15254015-Muscle Proteins, pubmed-meshheading:15254015-Muscular Dystrophies, pubmed-meshheading:15254015-Mutation, pubmed-meshheading:15254015-Phenotype, pubmed-meshheading:15254015-RNA, Messenger, pubmed-meshheading:15254015-Sarcolemma
pubmed:year
2004
pubmed:articleTitle
Disruption of muscle membrane and phenotype divergence in two novel mouse models of dysferlin deficiency.
pubmed:affiliation
Day Laboratory for Neuromuscular Research, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA. dmshmf@nccs.com.sg
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't