title: In vivo study of an aberrant dystrophin exon inclusion in X-linked dilated cardiomyopathy.
abstract: We previously identified a dystrophin intron 11 rearrangement in one family with X-linked dilated cardiomyopathy, causing incorporation of an aberrant exon in a tissue-specific manner. In this study we analyzed the role of different intron 11 genomic regions in the regulation of splicing by using mini-genes based approach, in C2C12 (skeletal muscle) myoblasts and myotubes, H9C2 cardiomyocytes, and HeLa cells. We show that inclusion of the aberrant exon is favored in H9C2 and differentiated C2C12 myotubes. These data suggest that the aberrant exon undergoes a differentiation-specific splicing. Unexpectedly, length of intron has a favorable effect in inclusion of the aberrant exon in the cardiac cells, suggesting that cardiac cells might be more prone to steric hindrance of trans-acting factors, involved in the inclusion of the aberrant exon. Furthermore, the cultured cell system used can serve as a suitable model to study human alternative splicing.
authors.affiliation: Dubowitz Neuromuscular Unit, Department of Paediatrics, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK.
authors.forename: Niaz
authors.initials: N
authors.lastname: Cohen
authors.forename: Paola
authors.initials: P
authors.lastname: Rimessi
authors.forename: Francesca
authors.initials: F
authors.lastname: Gualandi
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ferlini
authors.forename: Francesco
authors.initials: F
authors.lastname: Muntoni
mesh_terms: D017398:Alternative Splicing / Q000235:genetics; D020087:Alu Elements / Q000235:genetics; D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000235:genetics*; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D064211:Connectin; D016189:Dystrophin / Q000235:genetics*; D005091:Exons / Q000235:genetics*; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D007438:Introns / Q000235:genetics; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D009124:Muscle Proteins / Q000096:biosynthesis; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism; D032446:Myoblasts / Q000166:cytology / Q000502:physiology; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology / Q000502:physiology; D011494:Protein Kinases / Q000096:biosynthesis; D051381:Rats; D014162:Transfection
chemical_list: D064211:Connectin; D016189:Dystrophin; D009124:Muscle Proteins; C577285:TTN protein, human; D011494:Protein Kinases