Localization of dystrophin to postsynaptic regions of central nervous system cortical neurons.
Moderate non-progressive cognitive impairment is a consistent feature of Duchenne muscular dystrophy (DMD), although no central nervous system (CNS) abnormality has been identified. Recent studies have elucidated the molecular defect in DMD, including the absence of the protein dystrophin in affected individuals. Normal brain tissue contains dystrophin messenger RNA and dystrophin is present in low abundance in the brain and seems to be regulated in this tissue, at least in part, by a promoter that differs from that in muscle. 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.
Lidov
H G
HG
Department of Pathology, Children's Hospital Medical Center, Boston, Massachusetts.
Byers
T J
TJ
Watkins
S C
SC
Kunkel
L M
LM
D000818:Animals; D002462:Cell Membrane / Q000737:chemistry; D002525:Cerebellar Cortex / Q000737:chemistry*; D002540:Cerebral Cortex / Q000737:chemistry*; D016189:Dystrophin / Q000032:analysis*; D005455:Fluorescent Antibody Technique; D015151:Immunoblotting; D007150:Immunohistochemistry; D051379:Mice; D016253:Microscopy, Immunoelectron; D009137:Muscular Dystrophy, Animal / Q000378:metabolism*; D009474:Neurons / Q000737:chemistry*; D011689:Purkinje Cells / Q000737:chemistry; D013569:Synapses / Q000737:chemistry*; D014018:Tissue Distribution
D016189:Dystrophin