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BRGSF-HIS mice models

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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.

Oncodesign Services supports your preclinical needs with the development of tailor-made humanized models


Oncodesign Services continues to adopt the latest humanization approaches in order to remain a leader and expert CRO in humanized mouse studies, including BRGSF-HIS mice models, for preclinical pharmacological modeling. We have extensive experience in handling drug candidates of very different natures and mechanisms of action: small molecules, antibodies and derivatives, peptides and proteins, gene and cell therapies, vaccines and combinations thereof.

All our in vivo pharmacology studies are standardized and use reference drugs and positive controls for quality purposes. Also, all of our sites and in-vivo departments maintain full AAALAC International accreditation of our animal care and use program.


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