title: Development of atherosclerosis in Balb/c apolipoprotein E-deficient mice.
abstract: BACKGROUND
  Since its creation in 1992 by gene inactivation via gene targeting, the apolipoprotein E "knockout" mouse has become the most widely used rodent model for the study of atherosclerosis. Commercially available apolipoprotein E(-/-) mice are bred on a C57BL/6J background. The goal of the present study was to investigate the development of atherosclerosis in apolipoprotein E-deficient mice generated on a Balb/c background.
  
  
  METHODS
  We compared serum cholesterol concentrations and the development of atherosclerotic lesions in heterozygous Balb/c [apolipoprotein E(+/-)] mice fed regular rodent chow, Balb/c apolipoprotein E-deficient mice fed regular chow, and Balb/c apolipoprotein E-deficient mice fed a high-fat diet for up to 30 weeks. Expression of the chemokine JE (murine homologue of MCP-1), as well as the adhesion molecules E-selectin, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1, in the aortas of knockout mice fed a high-fat diet was measured by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  Balb/c apolipoprotein E-deficient mice develop atherosclerotic lesions in a reproducible temporal and morphological pattern. Total serum cholesterol concentrations in Balb/c apolipoprotein E-deficient mice fed regular chow or a high-fat diet, respectively, closely parallel those reported for C57BL/6J apolipoprotein E-deficient mice. The expression of all three adhesion molecules in the aorta follows a similar temporal pattern, peaking in the first 15 weeks, whereas JE concentrations peak around 23 weeks.
  
  
  CONCLUSIONS
  The availability of Balb/c apolipoprotein E-deficient mice will facilitate the study of atherosclerosis in a mouse strain that can concomitantly develop other pathological states that are not readily inducible in mice with the C57BL/6J background.
authors.affiliation: Department of Pathology, University of Michigan Medical School, 1301 Catherine Street, Ann Arbor, MI 48109-0602, USA. desai@med.umich.edu
authors.forename: Anjali
authors.initials: A
authors.lastname: Desai
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhao
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Warren
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency* / Q000502:physiology; D050197:Atherosclerosis / Q000097:blood / Q000235:genetics / Q000473:pathology*; D018932:Chemokine CCL2 / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D003331:Coronary Vessels / Q000378:metabolism / Q000473:pathology; D004041:Dietary Fats / Q000008:administration & dosage; D004195:Disease Models, Animal; D019040:E-Selectin / Q000378:metabolism; D015870:Gene Expression; D020868:Gene Silencing; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D014811:Vitamin E Deficiency / Q000097:blood / Q000235:genetics / Q000473:pathology*
chemical_list: D001057:Apolipoproteins E; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D004041:Dietary Fats; D019040:E-Selectin; C090509:Icam1 protein, mouse; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D002784:Cholesterol