| First Author | Grounds MD | Year | 2014 |
| Journal | Am J Pathol | Volume | 184 |
| Issue | 6 | Pages | 1668-76 |
| PubMed ID | 24685690 | Mgi Jnum | J:210966 |
| Mgi Id | MGI:5572978 | Doi | 10.1016/j.ajpath.2014.02.005 |
| Citation | Grounds MD, et al. (2014) Lipid accumulation in dysferlin-deficient muscles. Am J Pathol 184(6):1668-76 |
| abstractText | 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/J(dys-/-) 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/J(dys-/-) 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/J(dys-/-) 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-delta, in 3-month-old A/J(dys-/-) 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. |
