Analysis of glomerular lesions in an experimental model induced by apolipoprotein E gene.

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(1) Virus-mediated transduction of apolipoprotein B (apoE) in apoE-deficient mice : We injected recombinant adenoviruses containing apoE-Sendai into apoE-deficient mice, produced a model of lipoprotein glomerulopathy (LPG) and studied lipoprotein profiles and pathological findings. We prepared control groups by the injections of adenoviruses containing apoE2, 3 and 4, respectively.(2) Biochemical analysis in plasma : By the apoE-contained vectors, apoEs were expressed and the levels of total cholesterol (TC) and LDL were normalized. ApoE-Sendai-administered mice showed temporary hypertriglyceridemia and insufficient ameliorations of TC and LDL. Particularly, electronegative LDL, which formed a peak in capillary isotachoelectroporesis and consisted with oxidized-LDL, is marked. Accordingly, it is presumed that oxidized LDL plays a pathological role in LPG.(3) Pathological findings : Pathological findings were investigated by Sudan III stain on osmium-fixed specimens as well as by light microscopy and electron microscopy. In some mice given apoE-Sendai, lipoprotein accumulation of lipoproteins was found in the paramesangial area and around the vascular pole. These findings showed that the glomerular lesions mimicked those of LPG in human.(4) Analysis of apoE and FcRγ-chain deficient mice : It is reported that GVH disease in FcRγ-chain deficient mice shows lipoprotein thrombi containing apoE similar with those of LPG. We will try to breed apoE and FcRγ-chain double deficient mice and study the pathogenesis of LPG by the administration of adenovirus vectors containing apoE genes into the double deficient mice.