A latent defect in lymphoid-biased hematopoietic stem cells in UBC-GFP transgenic mice

Abstract

We used transgenic mice expressing GFP under the human ubiquitin promoter (UBC-GFP mice; Schaefer et al, 2001) in experiments studying a spontaneous recovery of hematopoiesis damaged by submyeloablative irradiation. Results were strikingly different from corresponding experiments that used two congenic strains of mice CD45.2 and CD45.1. Analysis of this unexpected difference in results revealed that while UBC-GFP mice have normal hematopoiesis that also regenerates normally after damage, they are inferior when competing with transplanted bone marrow from wild-type mice (CD45.1 or CD45.2). Interestingly, UBC-GFP mice engrafted transplanted bone marrow of wild-type mice without conditioning, and their conditioning with a low sublethal dose of irradiation resulted in an inappropriately high level of engraftment of transplanted bone marrow of wild-type donors. Interestingly also, the wild-type mice origin hematopoietic and blood cells were consistently more represented in the peripheral blood, spleen and thymus as compared to the bone marrow. Transplanted bone marrow contributed both to myelopoiesis and lymphopoiesis but their contribution was significantly higher in the lymphoid cells. Chimeric hematopoiesis resulting from the transplantation of wild-type bone marrow to UBC-GFP recipients could be transplanted to secondary recipients confirming a defect in the lymphoid-biased hematopoietic stem cells in UBC-GFP mice. Schaefer BC, Schaefer ML, Kappler JW, Marrack P, Kedl RM: Observation of antigen-dependent CD8+ T-cell/ dendritic cell interactions in vivo. Cell Immunol. 2001 Dec 15;214(2):110-22. Research was supported by the Grant Agency od the Czech Republic (GACR 17-01897S).