Cellular localization of the Huntington's disease protein and discrimination of the normal and mutated form.
Huntington's disease (HD) results from the expansion of a polyglutamine encoding CAG repeat in a gene of unknown function. The wide expression of this transcript does not correlate with the pattern of neuropathology in HD. To study the HD gene product (huntingtin), we have developed monoclonal antibodies raised against four different regions of the protein. On western blots, these monoclonals detect the approximately 350 kD huntingtin protein in various human cell lines and in neural and non-neural rodent tissues. In cell lines from HD patients, a doublet protein is detected corresponding to the mutated and normal huntingtin. Immunohistochemical studies in the human brain using two of these antibodies detects the huntingtin in perikarya of some neurons, neuropiles, varicosities and as punctate staining likely to be nerve endings.
Trottier
Y
Y
Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS, INSERM, ULP, Illkirch, France.
Devys
D
D
Imbert
G
G
Saudou
F
F
An
I
I
Lutz
Y
Y
Weber
C
C
Agid
Y
Y
Hirsch
E C
EC
Mandel
J L
JL
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D002460:Cell Line; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D018076:DNA, Complementary; D005260:Female; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000235:genetics* / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D009687:Nuclear Proteins / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000276:immunology; D012091:Repetitive Sequences, Nucleic Acid; D014018:Tissue Distribution; D014162:Transfection
D000911:Antibodies, Monoclonal; D018076:DNA, Complementary; C086055:HTT protein, human; C506812:Htt protein, mouse; C499524:Htt protein, rat; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins