title: Characterization of mouse myotilin and its promoter.
abstract: Myotilin is a sarcomeric protein mutated in two forms of muscle disease, limb-girdle muscular dystrophy type 1A and myofibrillar myopathy. Myotilin is expressed late during human myofibrillogenesis and localizes to Z-discs in mature sarcomere. It interacts with alpha-actinin, actin, and filamin C, and has strong F-actin-bundling activity. These features suggest an important role for myotilin in sarcomere organization. In our effort towards the construction of a genetic model for myotilin-related muscle disorders, we have cloned mouse myotilin, including its promoter region, and studied the expression in various tissues. Mouse myotilin is 90% identical with the human orthologue. Northern blot analysis revealed strong mRNA transcripts in skeletal and cardiac muscle, and weak expression in liver and lung tissue. Western blot and RT-PCR analysis showed the presence of one major product in mouse tissues. Analysis of the 5'-flanking region revealed a number of putative regulatory elements that drive expression in differentiating myoblasts. Finally, endogenous myotilin is induced at later stages of Z-disc assembly in C(2)C(12) cells indicating conservation between mouse and human promoter region.
authors.affiliation: Department of Pathology and Neuroscience Program, Biomedicum Helsinki, University of Helsinki, Finland.
authors.forename: Luca
authors.initials: L
authors.lastname: Mologni
authors.forename: Monica
authors.initials: M
authors.lastname: Moza
authors.forename: Maciej M
authors.initials: MM
authors.lastname: Lalowski
authors.forename: Olli
authors.initials: O
authors.lastname: Carpén
mesh_terms: D000375:Aging / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D064211:Connectin; D017124:Conserved Sequence; D003598:Cytoskeletal Proteins; D006801:Humans; D051379:Mice; D008840:Microfilament Proteins; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000235:genetics* / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D009136:Muscular Dystrophies / Q000235:genetics / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D009928:Organ Specificity; D011401:Promoter Regions, Genetic / Q000235:genetics; D020539:Sequence Analysis, Protein; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D014018:Tissue Distribution
chemical_list: D064211:Connectin; D003598:Cytoskeletal Proteins; C577290:MYOT protein, human; D008840:Microfilament Proteins; D009124:Muscle Proteins; C503771:Myot protein, mouse