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Comparative analysis of cortical gene expression in mouse models of Alzheimer's disease.
Neurobiol Aging. 2006 Mar; 27(3):377-86.NA

Abstract

Three mouse models of Alzheimer's disease (AD) were used to assess changes in gene expression potentially critical to amyloid beta-peptide (Abeta)-induced neuronal dysfunction. One mouse model harbored homozygous familial AD (FAD) knock-in mutations in both, amyloid precursor protein (APP) and presenilin 1 (PS-1) genes (APP(NLh/NLh)/PS-1(P264L/P264L)), the other two models harbored APP over-expression of FAD mutations (Tg2576) with the PS-1 knock-in mutation at either one or two alleles. These mouse models of AD had varying levels of Abeta40 and Abeta42 and different latencies and rates of Abeta deposition in brain. To assess changes in gene expression associated with Abeta accumulation, the Affymetrix murine genome array U74A was used to survey gene expression in the cortex of these three models both prior to and following Abeta deposition. Altered genes were identified by comparing the AD models with age-matched control littermates. Thirty-four gene changes were identified in common among the three models in mice with Abeta deposition. Among the up-regulated genes, three major classes were identified that encoded for proteins involved in immune responses, carbohydrate metabolism, and proteolysis. Down-regulated genes of note included pituitary adenylate cyclase-activating peptide (PACAP), brain-derived neurotrophic factor (BDNF), and insulin-like growth factor I receptor (IGF-IR). In young mice without detectable Abeta deposition, there were no regulated genes common among the three models, although 40 genes were similarly altered between the two Tg2576 models with the PS-1 FAD knock-in. Finally, changes in gene expression among the three mouse models of AD were compared with those reported in human AD samples. Sixty-nine up-regulated and 147 down-regulated genes were found in common with human AD brain. These comparisons across different genetic mouse models of AD and human AD brain provide greater support for the involvement of identified gene expression changes in the neuronal dysfunction and cognitive deficits accompanying amyloid deposition in mammalian brain.

Authors+Show Affiliations

Cephalon, Inc., Neurobiology, 145 Brandywine Parkway, West Chester, PA 19380-4245, USA. zwu@cephalon.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

15927307

Citation

Wu, Zhi-Liang, et al. "Comparative Analysis of Cortical Gene Expression in Mouse Models of Alzheimer's Disease." Neurobiology of Aging, vol. 27, no. 3, 2006, pp. 377-86.
Wu ZL, Ciallella JR, Flood DG, et al. Comparative analysis of cortical gene expression in mouse models of Alzheimer's disease. Neurobiol Aging. 2006;27(3):377-86.
Wu, Z. L., Ciallella, J. R., Flood, D. G., O'Kane, T. M., Bozyczko-Coyne, D., & Savage, M. J. (2006). Comparative analysis of cortical gene expression in mouse models of Alzheimer's disease. Neurobiology of Aging, 27(3), 377-86.
Wu ZL, et al. Comparative Analysis of Cortical Gene Expression in Mouse Models of Alzheimer's Disease. Neurobiol Aging. 2006;27(3):377-86. PubMed PMID: 15927307.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Comparative analysis of cortical gene expression in mouse models of Alzheimer's disease. AU - Wu,Zhi-Liang, AU - Ciallella,John R, AU - Flood,Dorothy G, AU - O'Kane,Teresa M, AU - Bozyczko-Coyne,Donna, AU - Savage,Mary J, Y1 - 2005/05/31/ PY - 2004/10/20/received PY - 2005/01/28/revised PY - 2005/02/09/accepted PY - 2005/6/2/pubmed PY - 2006/4/14/medline PY - 2005/6/2/entrez SP - 377 EP - 86 JF - Neurobiology of aging JO - Neurobiol Aging VL - 27 IS - 3 N2 - Three mouse models of Alzheimer's disease (AD) were used to assess changes in gene expression potentially critical to amyloid beta-peptide (Abeta)-induced neuronal dysfunction. One mouse model harbored homozygous familial AD (FAD) knock-in mutations in both, amyloid precursor protein (APP) and presenilin 1 (PS-1) genes (APP(NLh/NLh)/PS-1(P264L/P264L)), the other two models harbored APP over-expression of FAD mutations (Tg2576) with the PS-1 knock-in mutation at either one or two alleles. These mouse models of AD had varying levels of Abeta40 and Abeta42 and different latencies and rates of Abeta deposition in brain. To assess changes in gene expression associated with Abeta accumulation, the Affymetrix murine genome array U74A was used to survey gene expression in the cortex of these three models both prior to and following Abeta deposition. Altered genes were identified by comparing the AD models with age-matched control littermates. Thirty-four gene changes were identified in common among the three models in mice with Abeta deposition. Among the up-regulated genes, three major classes were identified that encoded for proteins involved in immune responses, carbohydrate metabolism, and proteolysis. Down-regulated genes of note included pituitary adenylate cyclase-activating peptide (PACAP), brain-derived neurotrophic factor (BDNF), and insulin-like growth factor I receptor (IGF-IR). In young mice without detectable Abeta deposition, there were no regulated genes common among the three models, although 40 genes were similarly altered between the two Tg2576 models with the PS-1 FAD knock-in. Finally, changes in gene expression among the three mouse models of AD were compared with those reported in human AD samples. Sixty-nine up-regulated and 147 down-regulated genes were found in common with human AD brain. These comparisons across different genetic mouse models of AD and human AD brain provide greater support for the involvement of identified gene expression changes in the neuronal dysfunction and cognitive deficits accompanying amyloid deposition in mammalian brain. SN - 0197-4580 UR - https://www.unboundmedicine.com/medline/citation/15927307/Comparative_analysis_of_cortical_gene_expression_in_mouse_models_of_Alzheimer's_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0197-4580(05)00094-1 DB - PRIME DP - Unbound Medicine ER -