Increased Apoptosis of Myoblasts in Drosophila Model for the Walker-Warburg Syndrome
Open Access
- 13 July 2010
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 5 (7), e11557
- https://doi.org/10.1371/journal.pone.0011557
Abstract
Walker-Warburg syndrome, a progressive muscular dystrophy, is a severe disease with various kinds of symptoms such as muscle weakness and occasional seizures. The genes of protein O-mannosyltransferases 1 and 2 (POMT1 and POMT2), fukutin, and fukutin-related protein are responsible for this syndrome. In our previous study, we cloned Drosophila orthologs of human POMT1 and POMT2 and identified their activity. However, the mechanism of onset of this syndrome is not well understood. Furthermore, little is known about the behavioral properties of the Drosophila POMT1 and POMT2 mutants, which are called rotated abdomen (rt) and twisted (tw), respectively. First, we performed various kinds of behavioral tests and described in detail the muscle structures by using these mutants. The mutant flies exhibited abnormalities in heavy exercises such as climbing or flight but not in light movements such as locomotion. Defective motor function in mutants appeared immediately after eclosion and was exaggerated with aging. Along with motor function, muscle ultrastructure in the tw mutant was altered, as seen in human patients. We demonstrated that expression of RNA interference (RNAi) for the rt gene and the tw mutant was almost completely lethal and semi-lethal, respectively. Flies expressing RNAi had reduced lifespans. These findings clearly demonstrate that Drosophila POMT mutants are models for human muscular dystrophy. We then observed a high density of myoblasts with an enhanced degree of apoptosis in the tw mutant, which completely lost enzymatic activity. In this paper, we propose a novel mechanism for the development of muscular dystrophy: POMT mutation causes high myoblast density and position derangement, which result in apoptosis, muscle disorganization, and muscle cell defects.Keywords
This publication has 54 references indexed in Scilit:
- Changes in Temperature Preferences and Energy Homeostasis in Dystroglycan MutantsScience, 2009
- Synaptic Defects in aDrosophilaModel of Congenital Muscular DystrophyJournal of Neuroscience, 2008
- Dystroglycan and ProteinO-Mannosyltransferases 1 and 2 Are Required to Maintain Integrity ofDrosophilaLarval MusclesMolecular Biology of the Cell, 2007
- Dissecting muscle and neuronal disorders in a Drosophila model of muscular dystrophyThe EMBO Journal, 2007
- Perlecan and Dystroglycan act at the basal side of theDrosophilafollicular epithelium to maintain epithelial organizationDevelopment, 2006
- Dystroglycan down-regulation links EGF receptor signaling and anterior–posterior polarity formation in the Drosophila oocyteProceedings of the National Academy of Sciences of the United States of America, 2006
- Neural Circuitry that Governs Drosophila Male Courtship BehaviorCell, 2005
- Mutations of the POMT1 gene found in patients with Walker–Warburg syndrome lead to a defect of protein O-mannosylationBiochemical and Biophysical Research Communications, 2004
- A Bit-role for integrins in apoptosisNature, 2004
- Post-translational disruption of dystroglycan–ligand interactions in congenital muscular dystrophiesNature, 2002