Identification and characterization of a large human brain gene whose expression is increased in Alzheimer disease.
A cDNA clone that was isolated from a human substantia innominata cDNA library is described. By Northern hybridization analysis, a 15.5 kilobase (kb) transcript was identified by this clone in RNA samples from several brain regions, but not in RNA samples from white matter, liver or placenta. Hybridization to human genomic DNA revealed a pattern indicative of a single copy gene. DNA sequence analysis showed 3.0 kb of 3' untranslated region with no significant open reading frame. An additional cDNA clone, representing a section of an alternate form of this transcript, was isolated that contained an additional 1.5 kb at the 3' end. Using a nuclease protection assay, the expression of this gene was found to be increased by 30% in Alzheimer disease temporal cortex RNA samples compared to temporal cortex RNA samples from normal controls, but to be at equivalent levels in Alzheimer disease, as compared to normal control, substantia innominata RNA samples. This assay also showed that this gene was expressed at 3.5-fold higher levels in normal substantia innominata than in normal cerebellum. In situ hybridization analysis showed that the transcript could be detected in cerebellar neurons.
Kinsmen Laboratory of Neurological Research, Department of Psychiatry, University of British Columbia, Vancouver, Canada.
B E
BE
Boyes
D G
DG
Walker
P L
PL
McGeer
E G
EG
McGeer
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics*; D001483:Base Sequence; D015152:Blotting, Northern; D015139:Blotting, Southern; D001921:Brain / Q000502:physiology / Q000503:physiopathology*; D002795:Choline O-Acetyltransferase / Q000032:analysis; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics* / Q000302:isolation & purification; D005260:Female; D015723:Gene Library; D005796:Genes; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009928:Organ Specificity; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012016:Reference Values; D013377:Substantia Innominata / Q000502:physiology / Q000503:physiopathology*; D014158:Transcription, Genetic
D012313:RNA; D004247:DNA; D002795:Choline O-Acetyltransferase