Studies of the glomerular mesangium and the juxtaglomerular apparatus in the genetically diabetic mouse.
Intact and uninephrectomized genetically diabetic (db/db) mice (C57BL/KsJ) and their nondiabetic littermates (dm/m) had renal biopsies performed at 6 months of age. Renal tissues were studied by regular light microscopy and by a variety of immunohistochemical techniques. Intact db/db mice had peripheral mesangial thickening as compared to db/m mice. This thickening, predominantly due to increased mesangial matrix material, extended to the glomerular hilum and the extraglomerular mesangium of the juxtaglomerular apparatus. This abnormality was markedly increased an uninephrectomized db/db mice (db/db-UN) compared to intact db/db mice. Db/m-UN animals had slightly greater mesangial thickness than intact db/mice but less than that of db/db mice. Intact db/db mice had increased mesangial IgM staining compared to db/m mice and these differences were magnified by uninephrectomy. The IgM staining, especially in the diabetic mice, involved the peripheral mesangium and the glomerular hilum extending into extraglomerular mesangium and the distal tubule at the level of the macula densa. The tubular staining in the region of the juxtaglomerular apparatus was between the tubular basement membrane and the epithelial cells and between epithelial cells. The distal tubular epithelial cell cytoplasm also showed increased staining for IgM as the tubule coursed away from the glomerulus. These studies amplify the argument that alterations in glomerular hemodynamics influence the rate of development of diabetic glomerular lesions. Further, these diabetic mice appear to represent an important model for the study of mesangial macromolecular processing mechanisms.
D000818:Animals; D001485:Basement Membrane / Q000473:pathology; D001786:Blood Glucose; D001835:Body Weight; D002908:Chronic Disease; D003920:Diabetes Mellitus / Q000235:genetics / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D005455:Fluorescent Antibody Technique; D007075:Immunoglobulin M / Q000032:analysis; D007606:Juxtaglomerular Apparatus / Q000473:pathology*; D007678:Kidney Glomerulus / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009392:Nephrectomy
D001786:Blood Glucose; D007075:Immunoglobulin M