Localization of dystrophin to postsynaptic regions of central nervous system cortical neurons
- 1 December 1990
- journal article
- letter
- Published by Springer Science and Business Media LLC in Nature
- Vol. 348 (6303), 725-728
- https://doi.org/10.1038/348725a0
Abstract
MODERATE non-progressive cognitive impairment is a consistent feature of Duchenne muscular dystrophy (DMD)1,2, although no central nervous system (CNS) abnormality has been identified3. Recent studies have elucidated the molecular defect in DMD, including the absence of the protein dystrophin in affected individuals4. Normal brain tissue contains dystrophin messenger RNA5,6 and dystrophin is present in low abundance in the brain7 and seems to be regulated in this tissue, at least in part, by a promoter that differs from that in muscle8,9. Until now, antibodies and immunocytochemical methods used to demonstrate dystrophin at the plasma membrane of mouse and human muscle have proven inadequate to localize precisely dystrophin in the mammalian CNS. We have now made an antibody (anti 6-10) which is much more sensitive than those previously available to immunolabel dystrophin in the CNS. Using this antibody, we found that in the mouse, dystrophin is particularly abundant in the neurons of the cerebral and cerebellar cortices, and that it is localized at postsynaptic membrane specializations. Dystrophin may have a different role in neurons than in muscle, and an alteration at the synaptic level may be the basis of the cognitive impairment in DMD.Keywords
This publication has 19 references indexed in Scilit:
- Alternative splicing of human dystrophin mRNA generates isoforms at the carboxy terminusNature, 1989
- Dystrophin abnormalities in Duchenne/Becker muscular dystrophyNeuron, 1989
- Functional diversity among spectrin isoformsCell Motility, 1989
- Cell and fiber type distribution of dystrophinNeuron, 1988
- Localizing the gene productNature, 1988
- The complete sequence of dystrophin predicts a rod-shaped cytoskeletal proteinCell, 1988
- Expression of the Murine Duchenne Muscular Dystrophy Gene in Muscle and BrainScience, 1988
- Expression of the putative Duchenne muscular dystrophy gene in differentiated myogenic cell cultures and in the brainNature, 1988
- Dystrophin: The protein product of the duchenne muscular dystrophy locusCell, 1987
- THE CENTRAL NERVOUS SYSTEM IN DUCHENNE MUSCULAR DYSTROPHYBrain, 1969