Lipid Accumulation in Dysferlin-Deficient Muscles
dc.contributor.author | Grounds, M. | |
dc.contributor.author | Terrill, J. | |
dc.contributor.author | Crabb, Hannah | |
dc.contributor.author | Robertson, Terry | |
dc.contributor.author | Papadimitriou, J. | |
dc.contributor.author | Spuler, S. | |
dc.contributor.author | Shavlakadze, T. | |
dc.date.accessioned | 2017-01-30T11:35:41Z | |
dc.date.available | 2017-01-30T11:35:41Z | |
dc.date.created | 2015-02-01T20:00:57Z | |
dc.date.issued | 2014 | |
dc.identifier.citation | Grounds, M. and Terrill, J. and Crabb, H. and Robertson, T. and Papadimitriou, J. and Spuler, S. and Shavlakadze, T. 2014. Lipid Accumulation in Dysferlin-Deficient Muscles. American Journal of Pathology. 184 (6): pp. 1668-1676. | |
dc.identifier.uri | http://hdl.handle.net/20.500.11937/13236 | |
dc.identifier.doi | 10.1016/j.ajpath.2014.02.005 | |
dc.description.abstract |
Dysferlin is a membrane associated protein involved in vesicle trafficking and fusion. Defects in dysferlin result in limb-girdle muscular dystrophy type 2B and Miyoshi myopathy in humans and myopathy in A/Jdys/ and BLAJ mice, but the pathomechanism of the myopathy is not understood. Oil Red O staining showed many lipid droplets within the psoas and quadriceps muscles of dysferlin-deficient A/Jdys/ mice aged 8 and 12 months, and lipid droplets were also conspicuous within human myofibers from patients with dysferlinopathy (but not other myopathies). Electron microscopy of 8-month-old A/Jdys/ psoas muscles confirmed lipid droplets within myofibers and showed disturbed architecture of myofibers. In addition, the presence of many adipocytes was confirmed, and a possible role for dysferlin in adipocytes is suggested. Increased expression of mRNA for a gene involved in early lipogenesis, CCAAT/enhancer binding protein-δ, in 3-month-old A/Jdys/ quadriceps (before marked histopathology is evident), indicates early induction of lipogenesis/adipogenesis within dysferlin-deficient muscles. Similar results were seen for dysferlin-deficient BLAJ mice. These novel observations of conspicuous intermyofibrillar lipid and progressive adipocyte replacement in dysferlin-deficient muscles present a new focus for investigating the mechanisms that result in the progressive decline of muscle function in dysferlinopathies. | |
dc.publisher | Elsevier Inc. | |
dc.title | Lipid Accumulation in Dysferlin-Deficient Muscles | |
dc.type | Journal Article | |
dcterms.source.volume | 184 | |
dcterms.source.number | 6 | |
dcterms.source.startPage | 1668 | |
dcterms.source.endPage | 1676 | |
dcterms.source.issn | 0002-9440 | |
dcterms.source.title | American Journal of Pathology | |
curtin.department | School of Biomedical Sciences | |
curtin.accessStatus | Fulltext not available |