Journal article
Deletion of brain dystroglycan recapitulates aspects of congenital muscular dystrophy
Nature (London), Vol.418(6896), pp.422-425
2002
DOI: 10.1038/nature00838
PMID: 12140559
Abstract
Fukuyama congenital muscular dystrophy (FCMD), muscle–eye–brain disease (MEB), and Walker–Warburg syndrome are congenital muscular dystrophies (CMDs) with associated developmental brain defects1,2,3,4. Mutations reported in genes of FCMD2 and MEB5 patients suggest that the genes may be involved in protein glycosylation. Dystroglycan is a highly glycosylated component of the muscle dystrophin–glycoprotein complex6 that is also expressed in brain, where its function is unknown7. Here we show that brain-selective deletion of dystroglycan in mice is sufficient to cause CMD-like brain malformations, including disarray of cerebral cortical layering, fusion of cerebral hemispheres and cerebellar folia, and aberrant migration of granule cells. Dystroglycan-null brain loses its high-affinity binding to the extracellular matrix protein laminin, and shows discontinuities in the pial surface basal lamina (glia limitans) that probably underlie the neuronal migration errors. Furthermore, mutant mice have severely blunted hippocampal long-term potentiation with electrophysiologic characterization indicating that dystroglycan might have a postsynaptic role in learning and memory. Our data strongly support the hypothesis that defects in dystroglycan are central to the pathogenesis of structural and functional brain abnormalities seen in CMD.
Details
- Title: Subtitle
- Deletion of brain dystroglycan recapitulates aspects of congenital muscular dystrophy
- Creators
- Steven A MOORE - Department of Pathology, The University of Iowa, Iowa City, Iowa 52242-1101, United StatesFumiaki SAITO - Howard Hughes Medical Institute, Department of Physiology and Biophysics and Department of Neurology, The University of Iowa, Iowa City, Iowa 52242-1101, United StatesToshlnori HOSHI - Department of Physiology and Biophysics, The University of Iowa, Iowa City, Iowa 52242-1101, United StatesKevin P CAMPBELL - Howard Hughes Medical Institute, Department of Physiology and Biophysics and Department of Neurology, The University of Iowa, Iowa City, Iowa 52242-1101, United StatesJianguo CHEN - Department of Physiology and Biophysics, The University of Iowa, Iowa City, Iowa 52242-1101, United StatesDaniel E MICHELS - Howard Hughes Medical Institute, Department of Physiology and Biophysics and Department of Neurology, The University of Iowa, Iowa City, Iowa 52242-1101, United StatesMichael D HENRY - Howard Hughes Medical Institute, Department of Physiology and Biophysics and Department of Neurology, The University of Iowa, Iowa City, Iowa 52242-1101, United StatesAlbee MESSING - Waisman Center and Department of Pathobiological Sciences, University of Wisconsin, Madison, Wisconsin 53705-2280, United StatesRonald D COHN - Howard Hughes Medical Institute, Department of Physiology and Biophysics and Department of Neurology, The University of Iowa, Iowa City, Iowa 52242-1101, United StatesSusan E ROSS-BARTA - Department of Pathology, The University of Iowa, Iowa City, Iowa 52242-1101, United StatesSteve WESTRA - Department of Pathology, The University of Iowa, Iowa City, Iowa 52242-1101, United StatesRoger A WILLIAMSON - Department of Obstetrics and Gynecology, The University of Iowa, Iowa City, Iowa 52242-1101, United States
- Resource Type
- Journal article
- Publication Details
- Nature (London), Vol.418(6896), pp.422-425
- Publisher
- Nature Publishing; London
- DOI
- 10.1038/nature00838
- PMID
- 12140559
- ISSN
- 0028-0836
- eISSN
- 1476-4687
- Language
- English
- Date published
- 2002
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Pathology; Iowa Neuroscience Institute; Radiation Oncology; Obstetrics and Gynecology; Urology
- Record Identifier
- 9984020991502771
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