BRGSF Mice: a Translational Model for Studying Human Immune System Transplantation
In the context of the contruction of a human immune system in mice, the degree of immunodeficiency of the used animals is critical. Compared to NOG and NSG mice, BRGSF (Flt3-deficient BALB/c Rag2−/−Il2rg−/−SirpaNOD) mice show a similar level of immunodeficiency, with unique features affecting both the murine lymphoid and myeloid compartments. Indeed, if the three mouse strains lack mouse T, B and NK cells ,and exhibit xeno-tolerant phagocytes, only BRGSF mice show a defect in the generation of dendritic cells. Because this depletion is genetic, it remains stable throughout the animal’s life span.
As a consequence, BRGSF mice provide advantages for the in vivo study of human myeloid cell subsets which have a competitive advantage over their murine counterparts after xenotransplantation of human CD34+ hematopoietic stem cells. BRGSF mice with a reconstituted human immune system (BRGSF-HIS) constitute a translational model for the evaluation of inflammatory disease candidate treatments, whenever the presence of human cells is critical for target engagement.
Of a note, if necessary, the human dendritic cell compartment of BRGSF-HIS mice can be transiently boosted after the xenograft using the Flt-3L cytokine, a strategy that cannot be used in Flt3+/+ recipient mice (such as NSG and NGO mice) as Flt3-L is highly cross-reactive between mouse and human species. This strategy has been successfully used in vaccination settings to improve the generation of antigen-specific human T and B cell responses.
Figure 1. Schematic view of the technical steps for the generation of “Human Immune System” (HIS) mice harboring cellular components of the human hematolymphoid system.
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