Lipid Accumulation in Dysferlin-Deficient Muscles
MetadataShow full item record
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.
Showing items related by title, author, creator and subject.
Laing, N.; Dye, Danielle; Wallgren-Pettersson, C.; Richard, G.; Monnier, N.; Lillis, S.; Winder, T.; Lochmüller, H.; Graziano, C.; Mitrani-Rosenbaum, S.; Twomey, D.; Sparrow, J.; Beggs, A.; Nowak, K. (2009)The ACTA1 gene encodes skeletal muscle a-actin, which is the predominant actin isoform in the sarcomeric thin filaments of adult skeletal muscle, and essential, along with myosin, for muscle contraction. ACTA1 disease-causing ...
Kurniawan, Dede Indra (2007)Background. Muscle cramps are one of the adverse affects suffered by hypercholesterolemia patients who are treated with statins. Besides reducing cholesterol levels, statins also reduce coenzyme Q10 (CoQ10) blood levels. ...
Actin Nemaline Myopathy Mouse Reproduces disease, suggests other actin disease phenotypes and provides cautionary note on muscle transgene expressionRavenscroft, G.; Jackaman, Connie; Sewry, C.; Mcnamara, E.; Squire, S.; Potter, A.; Papadimitriou, J.; Griffiths, L.; Bakker, A.; Davies, K.; Laing, N.; Nowak, K. (2011)Mutations in the skeletal muscle a-actin gene (ACTA1) cause congenital myopathies including nemaline myopathy, actin aggregate myopathy and rod-core disease. The majority of patients with ACTA1 mutations have severe ...