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Compared to NOD-SCID and NSG, the BRGSF mouse represents the most adapted animal model to study and predict human immune responses in vivo.
Compared to traditional immunodeficient strains, such as NOD-SCID and NSG, the BRGSF mouse represents the most immunodeficient model generated to date, with defect of both the murine lymphoid and myeloid compartments, and thus represents a strongly adapted animal model for xenograft of human tumor and/or immune system.
This next-generation mouse is a unique preclinical model to study:
The BRGSF is the most immunodeficient mouse model generated to date, with defects in both myeloid and lymphoid compartments (Rag2-/-, IL 2RĪ³-/-, Flk2-/-). Here is its genetic background:
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The BRGSF carries multiple genetic defects, including mutations in:
The BRGSF mouse model represents a valuable tool for:
BALB/c genetic background
As such, these animals represent valuable tools to predict clinical response to certain anticancer drugs, and for long-term transplantation studies. Indeed, contrary to NOD and NOD-derived strains such as NSG and NOG, BRSGF mice do not carry the Prkdc mutation and, therefore, do not show the SCID side effect of high sensitivity to radiation, T-cell leakage, and increased incidence of thymic lymphoma formation.
NOD-specific polymorphic SIRPĪ±
This renders BRGSF mice highly permissive to human cell engraftment. SIRPĪ± is a transmembrane glycoprotein expressed on early hematopoietic progenitors, on myeloid cells such as macrophages and granulocytes, and on dendritic cells and neurons. It binds CD47, an immunoglobulin that acts as a self-marker for macrophages. Importantly, several studies have shown that Cd47ā/ā mouse hematopoietic cells grafted into wild-type mice, and into mice lacking T, B and NK cells, are rapidly āeatenā by macrophages, as are wild-type cells if the CD47āSIRPĪ± binding is disrupted. Polymorphisms in SIRPĪ± thereby represent a potent genetic determinant of human hematopoietic stem cell engraftment and host survival.
Fully functional complement cascade
Unlike NOG-based strains, where C5A is knockout, BRGSF mice possess a fully functional complement cascade.
Fat pad implantation of PDX CR-IC-022-P3or CR-LRB-004-P1 (fragments of 5mm x 5mm). Treatment: two injections of 5-FU (56mg/kg) r when tumors reached 100 mm3.
BRGSF are permissive to two colorectal PDX. 5-FU shows anti-tumor activity when administered at early time point or when tumor is established.
Front Immunol
JBMRplus
BRGSF-HIS & hFcĪ³R to assess cell depletion
BRGSF-HIS & myeloid cell compartment in CRS
BRGSF-HIS for myeloid-directed therapy assessment
CD3 and BRGSF-HIS to assess IrAEs
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