Print Email Facebook Twitter Integrative Biological Analysis of the APOE*3-Leiden Transgenic Mouse Title Integrative Biological Analysis of the APOE*3-Leiden Transgenic Mouse Author Clish, C.B. Davidov, E. Oresic, M. Plasterer, T.N. Lavine, G. Londo, T. Meys, M. Snell, P. Stochaj, W. Adourian, A. Zhang, X. Morel, N. Neumann, E. Verheij, E. Vogels, J.T.W.E. Havekes, L.M. Afeyan, N. Regnier, F. van der Greef, J. Naylor, S. TNO Preventie en Gezondheid Publication year 2004 Abstract Integrative (or systems biology) is a new approach to analyzing biological entities as integrated systems of genetic, genomic, protein, metabolite, cellular, and pathway events that are in flux and interdependent. Here, we demonstrate the application of intregrative biological analysis to a mammalian disease model, the apolipoprotein E3-Leiden (APO*E3) transgenic mouse. Mice selected for the study were fed a normal chow diet and sacrificed at 9 weeks of age-conditions under which they develop only mild type I and II atherosclerotic lesions. Hepatic mRNA expression analysis showed a 25% decrease in APO A1 and a 43% increase in liver fatty acid binding protein expression between transgenic and wild type control mice, while there was no change in PPAR-alpha expression. On-line high performance liquid chromatography-mass spectrometry quantitative profiling of tryptic digests of soluble liver proteins and liver lipids, coupled with principle component analysis, enabled rapid identification of early protein and metabolite markers of disease pathology. These included a 44% increase in L-FABP in transgenic animals compared to controls, as well as an increase in triglycerides and select bioactive lysophosphatidylcholine species. A correlation analysis of identified genes, proteins, and lipids was used to construct an interaction network. Taken together, these results indicate that integrative biology is a powerful tool for rapid identification of early markers and key components of pathophysiologic processes, and constitute the first application of this approach to a mammalian system. Subject Biology PharmacologyAnalytical researchBiomedical researchDNAFatty acid binding proteinLipidLiver proteinLysophosphatidylcholineMessenger RNAPeroxisome proliferator activated receptor alphaProteinTriacylglycerolAnimal modelAnimal tissueControlled studyGeneGene expressionHigh performance liquid chromatographyMass spectrometryMouseNonhumanPrincipal component analysisTransgenic mouseAnimalsApolipoprotein E3Apolipoproteins EArteriosclerosisCarrier ProteinsChromatography, High Pressure LiquidChromatography, LiquidFatty Acid-Binding ProteinsGenomeHumansLipid MetabolismLiverLysophosphatidylcholinesMass SpectrometryMiceMice, TransgenicModels, BiologicalMultivariate AnalysisOligonucleotide Array Sequence AnalysisReceptors, Cytoplasmic and NuclearRNARNA, MessengerTranscription FactorsTrypsinAnimaliaMammaliaMus musculus To reference this document use: http://resolver.tudelft.nl/uuid:ddbd86fa-20ed-4642-bead-1d2fa9579f3a DOI https://doi.org/10.1089/153623104773547453 TNO identifier 237717 ISSN 1536-2310 Source OMICS A Journal of Integrative Biology, 8 (1), 3-13 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.