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Arachidonic acid/docosahexaenoic acid-supplemented diet in early life reduces body weight gain, plasma lipids, and adiposity in later life in ApoE*3 Leiden mice

Wielinga, P.Y., (author), Harthoorn, L.F., (author), Verschuren, L., (author), Schoemaker, M.H., (author), Jouni, Z.E., (author), van, Tol, E.A.F. (author), Kleemann, R., (author), Kooistra, T. (author)

Scope: This study addresses whether early life arachidonic acid (ARA)/docosahexaenoic acid (DHA) supplementation or eicosapentaenoic acid (EPA)/DHA (Omacor) supplementation affects body weight gain, lipid metabolism, and adipose tissue quantity and quality in later life in ApoE*3Leiden-transgenic mice, a humanized model for hyperlipidemia and...

article 2012

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PXR agonism decreases plasma HDL levels in ApoE*3-Leiden.CETP mice

de Haan, W. (author), de Vries-van der Weij, J. (author), Mol, I.M. (author), Hoekstra, M. (author), Romijn, J.A. (author), Jukema, J.W. (author), Havekes, L.M. (author), Princen, H.M.G. (author), Rensen, P.C.N. (author), TNO Kwaliteit van Leven (author)

Pregnane X receptor (PXR) agonism has been shown to affect multiple steps in both the synthesis and catabolism of HDL, but its integrated effect on HDL metabolism in vivo remains unclear. The aim of this study was to evaluate the net effect of PXR agonism on HDL metabolism in ApoE*3-Leiden (E3L) and E3L.CETP mice, well-established models for...

article 2009

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Apolipoprotein CI inhibits scavenger receptor BI and increases plasma HDL levels in vivo

de Haan, W. (author), Out, R. (author), Berbée, J.F.P. (author), van der Hoogt, C.C. (author), Dijk, K.W.v. (author), van Berkel, T.J.C. (author), Romijn, J.A. (author), Wouter Jukema, J. (author), Havekes, L.M. (author), Rensen, P.C.N. (author), TNO Kwaliteit van Leven (author)

Apolipoprotein CI (apoCI) has been suggested to influence HDL metabolism by activation of LCAT and inhibition of HL and CETP. However, the effect of apoCI on scavenger receptor BI (SR-BI)-mediated uptake of HDL-cholesteryl esters (CE), as well as the net effect of apoCI on HDL metabolism in vivo is unknown. Therefore, we evaluated the effect of...

article 2008

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Transgenic flavonoid tomato intake reduces C-reactive protein in human C-reactive protein transgenic mice more than wild-type tomato

Rein, D. (author), Schijlen, E. (author), Kooistra, T. (author), Herbers, K. (author), Verschuren, L. (author), Hall, R. (author), Sonnewald, U. (author), Bovy, A. (author), Kleemann, R. (author), TNO Kwaliteit van Leven TNO Voeding (author)

The increased consumption of fruits and vegetables is associated with reduced cardiovascular disease. The molecular basis of this health effect is not fully understood, yet dietary flavonoids are thought to play an important role. Genetic engineering has enabled us to overexpress specific flavonoids (flavones and flavonols) in tomato fruit....

article 2006

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Human CD46-transgenic mice in studies involving replication-incompetent adenoviral type 35 vectors

Verhaagh, S. (author), de Jong, E. (author), Goudsmit, J. (author), Lecollinet, S. (author), Gillissen, G. (author), de Vries, M. (author), van Leuven, K. (author), Que, I. (author), Ouwehand, K. (author), Mintardjo, R. (author), Weverling, G.J. (author), Radošević, K. (author), Richardson, J. (author), Eloit, M. (author), Lowik, C. (author), Quax, P. (author), Havenga, M. (author), TNO Kwaliteit van Leven (author)

Wild-type strains of mice do not express CD46, a high-affinity receptor for human group B adenoviruses including type 35. Therefore, studies performed to date in mice using replication-incompetent Ad35 (rAd35) vaccine carriers may underestimate potency or result in altered vector distribution. Here, it is reported that CD46 transgenic mice (MYII...

article 2006

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Response of apolipoprotein E*3-Leiden transgenic mice to dietary fatty acids: Combining liver proteomics with physiological data

de Roos, B. (author), Duivenvoorden, I. (author), Rucklidge, G. (author), Reid, M. (author), Ross, K. (author), Lamers, R.J.A.N. (author), Voshol, P.J. (author), Havekes, L.M. (author), Teusink, B. (author), TNO Kwaliteit van Leven (author)

article 2005

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Carcinogenicity

Maurici, D. (author), Aardema, M. (author), Corvi, R. (author), Kleber, M. (author), Krul, C.A.M. (author), Laurent, C. (author), Loprieno, N. (author), Pasanen, M. (author), Pfuhler, S. (author), Phillips, B. (author), Prentice, D. (author), Sabbioni, E. (author), Sanner, T. (author), Vanparys, P. (author), TNO Kwaliteit van Leven (author)

article 2005

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Tumor necrosis factor-α plays an important role in restenosis development

Monraats, P.S. (author), Pires, N.M.M. (author), Schepers, A. (author), Agema, W.R.P. (author), Boesten, L.S.M. (author), de Vries, M.R. (author), Zwinderman, A.H. (author), de Maat, M.P.M. (author), Doevendans, P.A.F.M. (author), de Winter, R.J. (author), Tio, R.A. (author), Waltenberger, J. (author), 't Hart, L.M. (author), Frants, R.R. (author), Quax, P.H.A. (author), van Vlijmen, B.J.M. (author), Havekes, L.M. (author), van der Laarse, A. (author), van der Wall, E.E. (author), Jukema, J.W. (author), TNO Kwaliteit van Leven (author)

Genetic factors appear to be important in the restenotic process after percutaneous coronary intervention (PCI), as well as in inflammation, a pivotal factor in restenosis. TNFα, a key regulator of inflammatory responses, may exert critical influence on the development of restenosis after PCI. The GENetic DEterminants of Restenosis (GENDER)...

article 2005

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Apolipoprotein CI overexpression is not a relevant strategy to block cholesteryl ester transfer protein (CETP) activity in CETP transgenic mice

TNO Kwaliteit van Leven (author), Gautier, T. (author), Masson, D. (author), Jong, M.C. (author), Pais De Barros, J.P. (author), Duverneuil, L. (author), Le Guern, N. (author), Deckert, V. (author), Dumont, L. (author), Bataille, A. (author), Zak, Z. (author), Jiang, X.C. (author), Havekes, L.M. (author), Lagrost, L. (author)

ApoCI (apolipoprotein CI) is a potent inhibitor of plasma CETP [CE (cholesteryl ester) transfer protein]. The relevance of apoCI overexpression as a method for CETP blockade in vivo was addressed in the present study in CETPTg/apoCITg mice (mice expressing both human CETP and apoCI). Despite a significant reduction in specific CETP activity in...

article 2005

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Integrative Biological Analysis of the APOE*3-Leiden Transgenic Mouse

Clish, C.B. (author), Davidov, E. (author), Oresic, M. (author), Plasterer, T.N. (author), Lavine, G. (author), Londo, T. (author), Meys, M. (author), Snell, P. (author), Stochaj, W. (author), Adourian, A. (author), Zhang, X. (author), Morel, N. (author), Neumann, E. (author), Verheij, E. (author), Vogels, J.T.W.E. (author), Havekes, L.M. (author), Afeyan, N. (author), Regnier, F. (author), van der Greef, J. (author), Naylor, S. (author), TNO Preventie en Gezondheid (author)

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 ...

article 2004

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Evaluation of the Xpa-Deficient Transgenic Mouse Model for Short-Term Carcinogenicity Testing: 9-Month Studies with Haloperidol, Reserpine, Phenacetin, and D-Mannitol

Lina, B.A.R. (author), Woutersen, R.A. (author), Bruijntjes, J.P. (author), van Benthem, J. (author), van den Berg, J.A.H. (author), Monbaliu, J. (author), Thoolen, B.J.J.M. (author), Beems, R.B. (author), van Kreijl, C.F. (author), TNO Voeding (author)

As part of the international evaluation program coordinated by ILSI/HESI, the potential of DNA repair deficient Xpa-/- mice and the double knockout Xpa-/-.p53+/- mice for short term carcinogenicity assays was evaluated. For comparison also wild-type C57BL/6 mice (WT) were included in these studies. Four test compounds were administered to groups...

article 2004

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Phenotype characterisation using integrated gene transcript, protein and metabolite profiling

Orešič, M. (author), Clish, C.B. (author), Davidov, E.J. (author), Verheij, E. (author), Vogels, J. (author), Havekes, L.M. (author), Neumann, E. (author), Adourian, A. (author), Naylor, S. (author), van der Greef, J. (author), Plasterer, T. (author), TNO Preventie en Gezondheid (author)

Multifactorial diseases present a significant challenge for functional genomics. Owing to their multiple compartmental effects and complex biomolecular activities, such diseases cannot be adequately characterised by changes in single components, nor can pathophysiological changes be understood by observing gene transcripts alone. Instead, a...

article 2004

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Effects of amlodipine, atorvastatin and combination of both on advanced atherosclerotic plaque in APOE*3-Leiden transgenic mice

Gaubius Instituut TNO (author), van de Poll, S.W.E. (author), Delsing, D.J.M. (author), Jukema, J.W. (author), Princen, H.M.G. (author), Havekes, L.M. (author), Puppels, G.J. (author), van der Laarse, A. (author)

Combined treatment of statins and calcium channel blockers has been suggested to be superior to statin therapy alone. We quantified the anti-atherosclerotic potential of amlodipine, atorvastatin and their combination on existing atherosclerotic plaques in the aorta of APOE*3-Leiden transgenic mice. Sixty-two mice were fed a high cholesterol...

article 2003

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Apolipoprotein CI deficiency markedly augments plasma lipoprotein changes mediated by human cholesteryl ester transfer protein (CETP) in CETP transgenic/apoCI-knocked out mice

Gaubius Instituut TNO (author), Gautier, T. (author), Masson, D. (author), Jong, M.C. (author), Duverneuil, L. (author), Guern, N.L. (author), Deckert, V. (author), de Barros, J.P.P. (author), Dumont, L. (author), Bataille, A. (author), Zak, Z. (author), Jiang, X.C. (author), Tall, A.R. (author), Havekes, L.M. (author), Lagrost, L. (author)

Transgenic mice expressing human cholesteryl ester transfer protein (HuCETPTg mice) were crossed with apolipoprotein CI-knocked out (apoCI-KO) mice. Although total cholesterol levels tended to be reduced as the result of CETP expression in HuCETPTg heterozygotes compared with C57BL6 control mice (-13%, not significant), a more pronounced...

article 2002

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Stimulation of lipogenesis by pharmacological activation of the liver X receptor leads to production of large, triglyceride-rich very low density lipoprotein particles

Gaubius Instituut TNO (author), Grefhorst, A. (author), Elzinga, B.M. (author), Voshol, P.J. (author), Plösch, T. (author), Kok, T. (author), Bloks, V.W. (author), van der Sluijs, F.H. (author), Havekes, L.M. (author), Romijn, J.A. (author), Verkade, H.J. (author), Kuipers, F. (author)

The oxysterol-activated liver X receptor (LXR) provides a link between sterol and fatty acid metabolism; activation of LXR induces transcription of lipogenic genes. This study shows that induction of the lipogenic genes Srebp-1c, Fas, and Acc1 upon administration of the synthetic LXR agonist T0901317 to C57BL/6J mice (10 mg/kg/day, 4 days) is...

article 2002

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Very-low-density lipoprotein binding to the apolipoprotein E receptor 2 is enhanced by lipoprotein lipase, and does not require apolipoprotein E

Gaubius Instituut TNO (author), Tacken, P.J. (author), de Beer, F. (author), van Vark, L.C. (author), Havekes, L.M. (author), Hofker, M.H. (author), van Dijk, K.W. (author)

The apolipoprotein (apo)E receptor 2 (apoER2) is a recently cloned member of the low-density lipoprotein (LDL) receptor (LDLR) family, showing a high homology with both the LDLR and the very-low-density lipoprotein (VLDL) receptor (VLDLR). In the present study, the binding characteristics of the apoER2 with respect to apoE and lipoprotein lipase...

article 2000

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Induction of somatic mutations but not methylated DNA adducts in λlacZ transgenic mice by dichlorvos

Pletsa, V. (author), Steenwinkel, M.-J.S.T. (author), van Delft, J.H.M. (author), Baan, R.A. (author), Kyrtopoulos, S.A. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)

In order to examine the in vivo genotoxic activity of dichlorvos, λlacZ transgenic mice (Muta(TM)Mouse) were treated i.p. with single (4.4 or 11 mg/kg) or multiple (5x11 mg/kg) doses of this agent and sacrificed 4 h or 14 days post-treatment for DNA adduct measurement or mutant frequency analysis, respectively. Neither methylated DNA adducts nor...

article 1999

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Methyl bromide causes DNA methylation in rats and mice but fails to induce somatic mutations in λlacZ transgenic mice

Pletsa, V. (author), Steenwinkel, M.-J.S.T. (author), van Delft, J.H.M. (author), Baan, R.A. (author), Kyrtopoulos, S.A. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)

Following single or multiple oral treatments of rats or λlacZ transgenic mice with methyl bromide, methylated DNA adducts (N7- and/or O6-methylguanine) were found at comparable levels in various tissues, including among others the glandular stomach, the forestomach and the liver. Multiple rat treatment resulted in substantial decreases in the...

article 1998

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Gene-mutation assays in lambda-lacZ transgenic mice: Comparison of lacZ with endogenous genes in splenocytes and small intestinal epithelium

van Delft, J.H.M. (author), Bergmans, A. (author), van Dam, F.J. (author), Tates, A.D. (author), Howard, L. (author), Winton, D.J. (author), Baan, R.A. (author)

Comparison of results derived from transgenic animal gene-mutation assays with those from mutation analyses in endogenous genes is an important step in the validation of the former. We have used λlacZ transgenic mice to study alkylation-induced mutagenesis in vivo in (a) lacZ and hprt in spleen cells, and (b) lacZ and Dlb-1 in small intestine...

article 1998

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Use of transgenic mice in lipoprotein metabolism and atherosclerosis research

Havekes, L.M. (author), van Vlijmen, B.J.M. (author), Jong, M.C. (author), van Dijk, K.W. (author), Hofker, M.H. (author), Gaubius Instituut TNO (author)

In APOE*3-Leiden transgenic mice the atherosclerotic lesion size is correlated with plasma cholesterol. In these mice the plasma lipid levels are positively correlated with the relative amount of APOE 3-Leiden protein on the VLDL particle. The plasma cholesterol levels are influenced by diet, age and gender, mainly due to an effect of these...

article 1997