title: ApoE-/-Fas-/- C57BL/6 mice: a novel murine model simultaneously exhibits lupus nephritis, atherosclerosis, and osteopenia.
abstract: To establish a mouse model of accelerated atherosclerosis in lupus, we generated apolipoprotein E-deficient (apoE(-/-)) and Fas(lpr/lpr) (Fas(-/-)) C57BL/6 mice. On a normal chow diet, 5 month old apoE(-/-)Fas(-/-) mice had enlarged glomerular tuft areas, severe proteinuria, increased circulating autoantibody levels, and increased apoptotic cells in renal and vascular lesions compared with either single knockout mice. Also, double knockout mice developed increased atherosclerotic lesions but decreased serum levels of total and non-HDL cholesterol compared with apoE(-/-)Fas(+/+) littermates. Moreover, female apoE(-/-)Fas(-/-) mice had lower vertebral bone mineral density (BMD) and bone volume density (BV/TV) than age-matched female apoE(-/-)Fas(+/+) mice. Compared with apoE(-/-)Fas(+/+) and apoE(+/+)Fas(-/-) mice, apoE(-/-)Fas(-/-) mice had decreased circulating oxidized phospholipid (OxPL) content on apoB-100 containing lipoprotein particles and increased serum IgG antibodies to OxPL, which were significantly correlated with aortic lesion areas (r = 0.58), glomerular tuft areas (r = 0.87), BMD (r = -0.57), and BV/TV (r = -0.72). These results suggest that the apoE(-/-)Fas(-/-) mouse model might be used to study atherosclerosis and osteopenia in lupus. Correlations of IgG anti-OxPL with lupus-like disease, atherosclerosis, and bone loss suggested a shared pathway of these disease processes.
authors.affiliation: Division of Rheumatology, Department of Medicine, University of California, Los Angeles, CA, USA.
authors.forename: Xuebing
authors.initials: X
authors.lastname: Feng
authors.forename: Hongyun
authors.initials: H
authors.lastname: Li
authors.forename: Alexis A
authors.initials: AA
authors.lastname: Rumbin
authors.forename: Xuping
authors.initials: X
authors.lastname: Wang
authors.forename: Antonio
authors.initials: A
authors.lastname: La Cava
authors.forename: Katherine
authors.initials: K
authors.lastname: Brechtelsbauer
authors.forename: Lawrence W
authors.initials: LW
authors.lastname: Castellani
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Witztum
authors.forename: Aldons J
authors.initials: AJ
authors.lastname: Lusis
authors.forename: Betty P
authors.initials: BP
authors.lastname: Tsao
mesh_terms: D000818:Animals; D053299:Apolipoprotein B-100; D050197:Atherosclerosis / Q000209:etiology*; D001323:Autoantibodies / Q000097:blood; D015519:Bone Density; D001851:Bone Diseases, Metabolic / Q000209:etiology*; D004195:Disease Models, Animal; D005260:Female; D008181:Lupus Nephritis / Q000209:etiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010084:Oxidation-Reduction; D010743:Phospholipids / Q000097:blood / Q000276:immunology / Q000378:metabolism
chemical_list: D053299:Apolipoprotein B-100; D001323:Autoantibodies; D010743:Phospholipids