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

We have previously developed an in vivo experimental system for a bovi ne hemoprotozoan parasite, in which SCID mice were periodically transf used 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 proporti on always fluctuated significantly. In the present study, we aimed to deplete the mouse RBCs circulating in SCID mice and, thereby, to creat e SCID mice having complete Bo-RBC substitution. An anti-erythropoieti n rabbit serum, an anti-mouse RBC rabbit serum and 23 monoclonal anti- mouse RBC rat antibodies were prepared for this purpose. They were exa mined, after administration into SCID mice, for their ability to decre ase hematocrit value and also for any other adverse effect. A monoclon al antibody, clone 2E11, was found to have potent ability to induce cl earance of the mouse RBCs in SCID mice without causing toxic effects. SCID mice receiving this antibody together with periodic transfusion o f Bo-RBCs had their circulating RBCs completely substituted with Bo-RB Cs. 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.