Lipid Accumulation in Dysferlin-Deficient Muscles
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 stain...
| Main Authors: | , , , , , , |
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| Format: | Journal Article |
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Elsevier Inc.
2014
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| Online Access: | http://hdl.handle.net/20.500.11937/13236 |
| _version_ | 1848748293831524352 |
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| author | Grounds, M. Terrill, J. Crabb, Hannah Robertson, Terry Papadimitriou, J. Spuler, S. Shavlakadze, T. |
| author_facet | Grounds, M. Terrill, J. Crabb, Hannah Robertson, Terry Papadimitriou, J. Spuler, S. Shavlakadze, T. |
| author_sort | Grounds, M. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T07:02:45Z |
| format | Journal Article |
| id | curtin-20.500.11937-13236 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T07:02:45Z |
| publishDate | 2014 |
| publisher | Elsevier Inc. |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-132362017-09-13T14:56:51Z Lipid Accumulation in Dysferlin-Deficient Muscles Grounds, M. Terrill, J. Crabb, Hannah Robertson, Terry Papadimitriou, J. Spuler, S. Shavlakadze, T. 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. 2014 Journal Article http://hdl.handle.net/20.500.11937/13236 10.1016/j.ajpath.2014.02.005 Elsevier Inc. restricted |
| spellingShingle | Grounds, M. Terrill, J. Crabb, Hannah Robertson, Terry Papadimitriou, J. Spuler, S. Shavlakadze, T. Lipid Accumulation in Dysferlin-Deficient Muscles |
| title | Lipid Accumulation in Dysferlin-Deficient Muscles |
| title_full | Lipid Accumulation in Dysferlin-Deficient Muscles |
| title_fullStr | Lipid Accumulation in Dysferlin-Deficient Muscles |
| title_full_unstemmed | Lipid Accumulation in Dysferlin-Deficient Muscles |
| title_short | Lipid Accumulation in Dysferlin-Deficient Muscles |
| title_sort | lipid accumulation in dysferlin-deficient muscles |
| url | http://hdl.handle.net/20.500.11937/13236 |