The transgenic SAD mouse: a model of human sickle cell glomerulopathy.
The transgenic SAD mouse which expresses a modified sickle hemoglobin, Hb SAD, displays in vivo hemoglobin polymerization and erythrocyte sickling. In the presence study functional and morphological renal analyses were performed in SAD mice in order to compare the renal pathology of SAD mice with the human disease. The SAD mice display renal hemosiderosis, microvascular occlusions, vascular thrombosis, cortical infarcts and papillary necrosis. In the medulla, hemoglobin polymers could be observed with infrequent erythrocyte sickling, which may explain the absence of significant renal concentration defect, whereas in humans, the difference in the vascularization network leads to more extensive sickling. Most animals develop glomerular hypertrophy and mesangial sclerosis which increases in frequency and severity with age. The glomerular damage is associated with functional defects, including increased blood urea nitrogen levels and non-selective proteinuria. The glomerular lesions of SAD mice strikingly mimic sickle cell glomerulosclerosis, the most severe renal complication of sickle cell disease in humans. In summary, the SAD mouse is a valuable model of the thrombotic and glomerulosclerotic complications of human sickle cell glomerulopathy and can serve for pathophysiologic studies, and, eventually, for prevention and therapy investigation.
De Paepe
M E
ME
Institut de Recherches Cliniques de Montréal, Faculté de Médecine de l'Université de Montréal, Québec, Canada.
Trudel
M
M
D000755:Anemia, Sickle Cell / Q000150:complications* / Q000235:genetics; D000818:Animals; D003165:Complement System Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005455:Fluorescent Antibody Technique; D005923:Glomerulosclerosis, Focal Segmental / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D006451:Hemoglobin, Sickle / Q000235:genetics; D006984:Hypertrophy; D007074:Immunoglobulin G / Q000378:metabolism; D007668:Kidney / Q000502:physiology / Q000648:ultrastructure; D007678:Kidney Glomerulus / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic
D006451:Hemoglobin, Sickle; D007074:Immunoglobulin G; D003165:Complement System Proteins