RESUMEN
Dilated cardiomyopathy is a common complication of Duchenne and Becker muscular dystrophies, which are caused by mutations in the dystrophin gene. The mdx mouse is an animal model for Duchenne muscular dystrophy (DMD) and shows mildly dystrophic changes in the heart. By contrast, the utrophin-dystrophin knockout (dko) mouse shows severe dystrophic changes in cardiac muscle, that more closely resembles DMD cardiomyopathy than mdx mouse. However the pathogenesis of development has not been fully understood. Recently many reports have revealed that calcineurin and stress activated protein kinase (SAPK)/p38-mitogen activated protein kinase (MAPK) hypertrophic signalling pathways are associated with the development of some forms of hypertrophic and dilated cardiomyopathies. These signalling pathways may have some roles in the development of dystrophin-deficient cardiomyopathy. Here we report that calcineurin and SAPK/p38-MAPK signalling pathways were constantly activated in dko hearts, but the activation varied in mdx hearts. The pathogenesis of the development of dystrophin-deficient cardiomyopathy may be associated with the activation of these signalling pathways.
Asunto(s)
Calcineurina/metabolismo , Cardiomiopatía Dilatada/enzimología , Cardiomiopatía Dilatada/genética , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Distrofia Muscular de Duchenne/complicaciones , Miocardio/enzimología , Factores de Edad , Animales , Factor Natriurético Atrial/genética , Calcineurina/genética , Cardiomiopatía Dilatada/fisiopatología , Proteínas del Citoesqueleto/deficiencia , Proteínas del Citoesqueleto/genética , Distrofina/deficiencia , Distrofina/genética , Gliceraldehído-3-Fosfato Deshidrogenasas/genética , Proteínas de la Membrana/deficiencia , Proteínas de la Membrana/genética , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Proteína Quinasa 8 Activada por Mitógenos , Distrofia Muscular de Duchenne/genética , Miocardio/patología , Péptido Natriurético Encefálico , ARN Mensajero/metabolismo , Receptor de Angiotensina Tipo 1 , Receptor de Angiotensina Tipo 2 , Receptores de Angiotensina/genética , Transducción de Señal/genética , Utrofina , Proteínas Quinasas p38 Activadas por MitógenosRESUMEN
Differential display reverse transcription polymerase chain reaction (DD RT-PRC) was used to isolate cDNA clones of mRNA expressed in particular compartments of the developing murine head. One clone has been characterized and found to be the murine homologue of the MLP genes. In other species the LIM-domain containing MLPs are expressed specifically in muscle. In situ hybridization and RT-PCR have confirmed that the murine gene is expressed during both cardiac and skeletal myogenesis. Our data show that DD RT-PCR is a valuable technique to clone cDNA clones from minute tissue samples by virtue of the gene's expression pattern rather than by a process of library screening by homology.