Lipoprotein glomerulopathy induced by ApoE-Sendai is different from glomerular lesions in aged apoE-deficient mice

Abstract

Objective A mutant of apolipoproteinE (apoE), ApoE-Sendai (Arg145Pro), is one of the major causative factors of human lipoprotein glomerulopathy (LPG). An apoE-deficient mouse with introduced ApoE-Sendai gene (ApoE-Sendai mouse) developed a murine counterpart of LPG, whereas it was also reported that apoE-deficient mouse (apoE KO mouse) spontaneously developed LPG-like lesion regardless of introduction of ApoE-Sendai gene. In the present study, we differentiated renal lesions between these two models by detailed analyses of histology and lipoprotein profile, and clarified the role of apoE variants. Method ApoE-Sendai mice were induced by injection of adenovirus vectors. The kidneys showing LPG-like lesions in apoE-Sendai and apoE KO mice were histopathologically evaluated. Plasma lipids and lipoproteins of both mice were also examined. Results Histological alteration of the kidney in ApoE-Sendai mice was observed with light microscopy (in 40 out of 50 mice; mild 24, moderate 13, severe 3). Characteristic lesions were dilated vascular lumens mimicking lipoprotein thrombi in human LPG. Similar changes were found in hematoxylin-eosin stained sections of aged apoE KO mice. Meanwhile, periodic acid-Schiff, Azan Mallory, and Oil red O/Sudan III stained sections revealed that the dilated lumens of ApoE-Sendai mice mainly contained lipids and lipoproteins but those of aged apoE KO mice contained much other materials, e.g., proteins and fibrils. These findings were supported by electr…