DEVELOPMENT OF AN ANIMAL MODEL FOR HEMOLYTIC UREMIA SYNDROME (HUS) WITH NONHUMAN PRIMATES

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To develop an animal model for hemolytic uremia syndrome (HUS) using non-human primates, Cercopithecine monkeys such as African green monkeys (Cercopithecus aetiopus) and cynomolgus monkeys (Macaca fascicularis) were used in this experiment. The existence of a glycolipid receptor (ceramid trihexose ; CTH) for Vero toxins (VT1, VT2) was investigated by a biochemical method with thin layer chromatography. As a result, the receptors were more abundantly expressed in a cynomolgus monkey than an African green monkey and they localized mainly in the kidneys, spleen, bone marrow and lungs. Immunohistological studies by the use of a monoclonal antibody recognizing the CTH revealed that it was expressed densely in the mucosal epithelial cells of the small intestine, glomerulus and renal tubules in the kidneys and vascular endothelial cells in the medulla of the spleen and small blood vessels in the whole body. In the in vivo study, 24〜48hrs after Vero toxins (VT1 or VT2) injection, cynomolgus monkeys became moribund and they showed intestinal hemorrhage with thoracic fluid or ascite. Obvious thrombocytepenia, deterioration of a coagulation function and anomalies of the blood biochemical values were demonstrated. Histological examinations exhibited necrosis and severe hemorrhage in the intestinal mucosa, hemorrhage in the adrenal cortex, edematous change in the lungs, vacuolar degeneration of the vascular endothelial cells and degeneration of glomerulus and renal tubules in the kidneys, which are similar to clinicopathological lesions observed in human cases.