Dystrophin immunoreactivity in normal and Duchenne human fetal neurons in culture.
Dystrophin, the protein product defective in Duchenne muscular dystrophy (DMD), is present in all types of muscle and in the brain. The function of the protein is unknown and its role in the brain is unclear, although 30% of DMD patients show nonprogressive mental retardation. We have therefore studied the localisation of dystrophin in cultures of normal and DMD human fetal neurons using antibodies raised to different regions of the protein. Dystrophin immunoreactivity was demonstrated in the soma and axon hillock of normal neurons and appeared to be associated with the inner part of the cell membrane, although some intracellular staining was also observed. Positive dystrophin staining was present only in cells with fully developed neuronal features, although not all the neurons were positive. Glial cells were always negative for the antigen. Immunostaining with antibodies to the brain spectrins indicate that the dystrophin antibodies did not crossreact with these proteins. The possibility of cross-reactivity with other proteins is discussed. Studies of cells cultured from a DMD fetus also showed specific dystrophin immunostaining in neurons, although the muscle was generally negative for dystrophin. However, the localisation of dystrophin immunostaining and that of the brain spectrins and neurofilaments appeared abnormal, as did the overall morphology of the cells. This suggests that dystrophin may play a role during brain development and dystrophin deficiency results in abnormal neuronal features. This would be consistent with the nonprogressive nature of the mental retardation observed in DMD patients.
Torelli
S
S
Department of Cytomorphology, School of Medicine, Cagliari, Italy.
Sogos
V
V
Ennas
M G
MG
Muntoni
F
F
Clerk
A
A
Strong
P N
PN
Gremo
F
F
D015153:Blotting, Western; D002478:Cells, Cultured; D016189:Dystrophin / Q000378:metabolism*; D005333:Fetus / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D009136:Muscular Dystrophies / Q000196:embryology / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D012016:Reference Values; D013049:Spectrin / Q000378:metabolism; D013194:Staining and Labeling
D016189:Dystrophin; D013049:Spectrin