A method for rapid and complete substitution of the circulating erythrocytes in SCID mice with bovine erythrocytes and use of the substituted mice for bovine hemoprotozoa infections

Abstract

We have previously developed an in vivo experimental system for a bovine hemoprotozoan parasite, in which SCID mice were periodically transfused with bovine red blood cells (Bo-RBCs), followed by infection with the parasite. The SCID mice prepared by the original method, however, had both mouse and bovine RBCs in the circulation, and their proportion always fluctuated significantly. In the present study, we aimed to deplete the mouse RBCs circulating in SCID mice and, thereby, to create SCID mice having complete Bo-RBC substitution. An anti-erythropoietin rabbit serum, an anti-mouse RBC rabbit serum and 23 monoclonal anti-mouse RBC rat antibodies were prepared for this purpose. They were examined, after administration into SCID mice, for their ability to decrease hematocrit value and also for any other adverse effect. A monoclonal antibody, clone 2E11, was found to have potent ability to induce clearance of the mouse RBCs in SCID mice without causing toxic effects. SCID mice receiving this antibody together with periodic transfusion of Bo-RBCs had their circulating RBCs completely substituted with Bo-RBCs. Infection of Bo-RBC-SCID mice with bovine hemoprotozoan parasites demonstrated that elimination of the mouse RBCs from Bo-RBC-SCID mice resulted in augmentation of parasite growth.