Gene expression analysis in a transgenic Caenorhabditis elegans Alzheimer's disease model.
We have engineered transgenic Caenorhabditis elegans animals to inducibly express the human beta amyloid peptide (Abeta). Gene expression changes resulting from Abeta induction have been monitored by cDNA hybridization to glass slide microarrays containing probes for almost all known or predicted C. elegans genes. Using statistical criteria, we have identified 67 up-regulated and 240 down-regulated genes. Subsets of these regulated genes have been tested and confirmed by quantitative RT-PCR. To investigate whether genes identified in this model system also show gene expression changes in Alzheimer's disease (AD) brain, we have also used quantitative RT-PCR to examine in post-mortem AD brain tissue transcript levels of alphaB-crystallin (CRYAB) and tumor necrosis factor-induced protein 1 (TNFAIP1), human homologs of genes found to be robustly induced in the transgenic C. elegans model. Both CRYAB and TNFAIP1 show increased transcript levels in AD brains, supporting the validity of this approach.
Link
Christopher D
CD
Institute for Behavioral Genetics, University of Colorado, Campus Box 447, Boulder, CO 80309, USA. linkc@colorado.edu
Taft
Andrew
A
Kapulkin
Vadim
V
Duke
Kyle
K
Kim
Stuart
S
Fei
Qing
Q
Wood
Douglas E
DE
Sahagan
Barbara G
BG
D048868:Adaptor Proteins, Signal Transducing; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000032:analysis / Q000235:genetics*; D000818:Animals; D001923:Brain Chemistry / Q000235:genetics*; D017173:Caenorhabditis elegans / Q000235:genetics*; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000235:genetics; D005786:Gene Expression Regulation; D016678:Genome; D006360:Heat-Shock Proteins / Q000235:genetics; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D030781:Organisms, Genetically Modified / Q000235:genetics*; D011506:Proteins / Q000032:analysis*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection / Q000379:methods; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*; D015854:Up-Regulation / Q000235:genetics; D038203:alpha-Crystallin B Chain / Q000032:analysis*
D048868:Adaptor Proteins, Signal Transducing; D016229:Amyloid beta-Peptides; D006360:Heat-Shock Proteins; D011506:Proteins; D012333:RNA, Messenger; C115968:TNFAIP1 protein, human; D014409:Tumor Necrosis Factor-alpha; D038203:alpha-Crystallin B Chain