title: Hearts of dystonia musculorum mice display normal morphological and histological features but show signs of cardiac stress.
abstract: Dystonin is a giant cytoskeletal protein belonging to the plakin protein family and is believed to crosslink the major filament systems in contractile cells. Previous work has demonstrated skeletal muscle defects in dystonin-deficient dystonia musculorum (dt) mice. In this study, we show that the dystonin muscle isoform is localized at the Z-disc, the H zone, the sarcolemma and intercalated discs in cardiac tissue. Based on this localization pattern, we tested whether dystonin-deficiency leads to structural defects in cardiac muscle. Desmin intermediate filament, microfilament, and microtubule subcellular organization appeared normal in dt hearts. Nevertheless, increased transcript levels of atrial natriuretic factor (ANF, 66%) beta-myosin heavy chain (beta-MHC, 95%) and decreased levels of sarcoplasmic reticulum calcium pump isoform 2A (SERCA2a, 26%), all signs of cardiac muscle stress, were noted in dt hearts. Hearts from two-week old dt mice were assessed for the presence of morphological and histological alterations. Heart to body weight ratios as well as left ventricular wall thickness and left chamber volume measurements were similar between dt and wild-type control mice. Hearts from dt mice also displayed no signs of fibrosis or calcification. Taken together, our data provide new insights into the intricate structure of the sarcomere by situating dystonin in cardiac muscle fibers and suggest that dystonin does not significantly influence the structural organization of cardiac muscle fibers during early postnatal development.
authors.affiliation: Department of Biology, Laurentian University, Sudbury, Ontario, Canada.
authors.forename: Justin G
authors.initials: JG
authors.lastname: Boyer
authors.forename: Kunal
authors.initials: K
authors.lastname: Bhanot
authors.forename: Rashmi
authors.initials: R
authors.lastname: Kothary
authors.forename: Céline
authors.initials: C
authors.lastname: Boudreau-Larivière
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics*; D003598:Cytoskeletal Proteins / Q000235:genetics*; D003893:Desmin / Q000378:metabolism; D004422:Dystonia Musculorum Deformans / Q000235:genetics*; D000071821:Dystonin; D006321:Heart / Q000503:physiopathology; D007382:Intermediate Filaments / Q000378:metabolism; D051379:Mice; D008870:Microtubules / Q000378:metabolism; D009200:Myocardial Contraction; D009206:Myocardium / Q000473:pathology; D018995:Myosin Heavy Chains / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020033:Protein Isoforms; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics
chemical_list: D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D003893:Desmin; C095667:Dst protein, mouse; D000071821:Dystonin; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D009320:Atrial Natriuretic Factor; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D018995:Myosin Heavy Chains; C506947:Atp2a2 protein, mouse