Print Email Facebook Twitter Macrophage specific overexpression of the human macrophage scavenger receptor in transgenic mice, using a 180-kb yeast artificial chromosome, leads to enhanced foam cell formation of isolated peritoneal macrophages Title Macrophage specific overexpression of the human macrophage scavenger receptor in transgenic mice, using a 180-kb yeast artificial chromosome, leads to enhanced foam cell formation of isolated peritoneal macrophages Author de Winther, M.P.J. van Dijk, K.W. van Vlijmen, B.J.M. Gijbels, M.J.J. Heus, J.J. Wijers, E.R. van den Bos, A.C. Breuer, M. Frants, R.R. Havekes, L.M. Hofker, M.H. Gaubius instituut TNO Publication year 1999 Abstract Macrophage scavenger receptors class A (MSR) are thought to play an important role in atherogenesis by mediating the unrestricted uptake of modified lipoproteins by macrophages in the vessel wall leading to foam cell formation. To investigate the in vivo role of the MSR in this process, a transgenic mouse model expressing both isoforms of the human MSR was generated. A 180-kb yeast artificial chromosome (YAC) containing the human MSR gene (MSR1) with 60- and 40-kb flanking sequence at the 5' and 3' end, respectively, was obtained by reducing the size of a 1050-kb YAC by homologous recombination. This 180-kb YAC was microinjected into mouse oocytes. In the resulting transgenic mice, high levels of mRNA for both type I and type II human MSR1 were detected in peritoneal macrophages and trace levels in other organs, known to contain macrophage-derived cells. Using an antibody against the human MSR, the Kupffer cells in the liver were shown to contain the MSR protein. In vivo clearance of acetyl-LDL was not changed in the MSR1-transgenic mice. However, in vitro studies using peritoneal macrophages from the transgenic mice showed a two-fold increased degradation of acetyl-LDL and cholesterolester accumulation concomitant with a four-fold increase in foam cell formation, as compared to wild-type macrophages. Thus, macrophage specific overexpression of the MSR may lead to increased foam cell formation, which is one of the initial and crucial steps in atherogenesis. Copyright (C) 1999 Elsevier Science Ireland Ltd. Subject BiologyAcetyl-low density lipoproteinMacrophage scavenger receptorTransgenicsYeast artificial chromosomeacetyl low density lipoproteincholesterol esterscavenger receptoranimal cellanimal experimentarticleatherogenesiscell proliferationcontrolled studyfoam cellgene overexpressionimmunohistochemistrymousenonhumanperitoneum macrophagepriority journaltransgenic mouseyeast artificial chromosomeAnimalsBase SequenceCells, CulturedChromosomes, Artificial, YeastDisease Models, AnimalFoam CellsGene ExpressionHumansKupffer CellsLipoproteins, LDLMacrophages, PeritonealMiceMice, TransgenicMolecular Sequence DataPolymerase Chain ReactionReceptors, ImmunologicReceptors, ScavengerRNA, MessengerScavenger Receptors, Class ASensitivity and SpecificitySpecies SpecificityTissue Distribution To reference this document use: http://resolver.tudelft.nl/uuid:8cb48ddb-661f-4b13-b076-76ee14bc70ec DOI https://doi.org/10.1016/s0021-9150(99)00204-x TNO identifier 235153 ISSN 0021-9150 Source Atherosclerosis, 147 (2), 339-347 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.