Expression of multiple nebulin isoforms in human skeletal muscle and brain

Department of Neurology, University Hospital and University of Tampere, Tampere, FinlandAccepted 6 March 2012ABSTRACT: Introduction: Nebulin is a large actin-bindingprotein of the skeletal muscle sarcomere. Multiple isoforms ofnebulin are produced from the 183-exon–containing nebulingene (NEB). Mutations in NEB cause nemaline myopathy, distalmyopathy, and core-rod myopathy. Methods: Nebulin mRNAexpression was assessed by microarrays and RT-PCR in 21human leg muscle and 2 brain samples. Protein expressionwas assessed by immunohistochemistry in 5 regions of 1 brainsample. Results: Nebulin isoform diversity is as high in brainas in skeletal muscle. Isoforms with more than 22 super repeatsseem to be more common than previously anticipated. Immuno-histochemistry showed nebulin expression predominantly in thecytoplasm of pyramidal neurons but also in the cytoplasm ofmainly subcortical endothelial cells. Conclusions: Nebulin, asin skeletal muscle, may have a role as an actin filament stabi-lizer or length regulator in neurons of the human brain, althoughpatients with NEB mutations usually have normal cognition.