Integrative biological analysis of the APOE*3-leiden transgenic mouse

Clary B. Clish, E. Davidov, Matej Oresic, T. N. Plasterer, G. Lavine, T. Londo, M. Meys, P. Snell, W. Stochaj, A. Adourian, X. Zhang, N. Morel, E. Neumann, E. Verheij, J.T.W.E. Vogels, L. M. Havekes, N. Afeyan, F. Regnier, J. van der Greef, S. Naylor

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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.
Original languageEnglish
Pages (from-to)3 - 13
Number of pages11
JournalOMICS: A Journal of Integrative Biology
Volume8
Issue number1
DOIs
Publication statusPublished - 2004
MoE publication typeA1 Journal article-refereed

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Transgenic Mice
Metabolites
Liver
Proteins
Apolipoprotein E3
Lipids
PPAR alpha
Fatty Acid-Binding Proteins
Lysophosphatidylcholines
Genetically Modified Animals
Systems Biology
High performance liquid chromatography
Pathology
Nutrition
Mass spectrometry
Mass Spectrometry
Animals
Triglycerides
High Pressure Liquid Chromatography
Fluxes

Cite this

Clish, C. B., Davidov, E., Oresic, M., Plasterer, T. N., Lavine, G., Londo, T., ... Naylor, S. (2004). Integrative biological analysis of the APOE*3-leiden transgenic mouse. OMICS: A Journal of Integrative Biology, 8(1), 3 - 13. https://doi.org/10.1089/153623104773547453
Clish, Clary B. ; Davidov, E. ; Oresic, Matej ; 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. / Integrative biological analysis of the APOE*3-leiden transgenic mouse. In: OMICS: A Journal of Integrative Biology. 2004 ; Vol. 8, No. 1. pp. 3 - 13.
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Clish, CB, Davidov, E, Oresic, M, Plasterer, TN, Lavine, G, Londo, T, Meys, M, Snell, P, Stochaj, W, Adourian, A, Zhang, X, Morel, N, Neumann, E, Verheij, E, Vogels, JTWE, Havekes, LM, Afeyan, N, Regnier, F, van der Greef, J & Naylor, S 2004, 'Integrative biological analysis of the APOE*3-leiden transgenic mouse', OMICS: A Journal of Integrative Biology, vol. 8, no. 1, pp. 3 - 13. https://doi.org/10.1089/153623104773547453

Integrative biological analysis of the APOE*3-leiden transgenic mouse. / Clish, Clary B.; Davidov, E.; Oresic, Matej; 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.

In: OMICS: A Journal of Integrative Biology, Vol. 8, No. 1, 2004, p. 3 - 13.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Integrative biological analysis of the APOE*3-leiden transgenic mouse

AU - Clish, Clary B.

AU - Davidov, E.

AU - Oresic, Matej

AU - Plasterer, T. N.

AU - Lavine, G.

AU - Londo, T.

AU - Meys, M.

AU - Snell, P.

AU - Stochaj, W.

AU - Adourian, A.

AU - Zhang, X.

AU - Morel, N.

AU - Neumann, E.

AU - Verheij, E.

AU - Vogels, J.T.W.E.

AU - Havekes, L. M.

AU - Afeyan, N.

AU - Regnier, F.

AU - van der Greef, J.

AU - Naylor, S.

PY - 2004

Y1 - 2004

N2 - 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.

AB - 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.

U2 - 10.1089/153623104773547453

DO - 10.1089/153623104773547453

M3 - Article

VL - 8

SP - 3

EP - 13

JO - OMICS: A Journal of Integrative Biology

JF - OMICS: A Journal of Integrative Biology

SN - 1536-2310

IS - 1

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