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immunodeficient-brgsf-mice

Strain Name: BALB/c Rag2tm1Fwa Il2rgtm1Cgn SirpaNOD Flk2tm1lrl

BALB/c Rag2tm1Fwa Il2rgtm1Cgn SirpaNOD Flk2tm1lrl
  • ● A powerful tool for complement-dependent cytotoxicity (CDC) studies because of the presence of a functional CDC system in vivo.
    Unlike N*G mice, BRGSF mice with BALB/c background, which has a complete complement cascade in vivo, which is a powerful tool for complement-dependent cytotoxicity (CDC) studies. For example, efficacy and safety assessment of cellular immunotherapy (e.g., CAR-T).
  • ● One of the most highly immunodeficient mouse models on the current market, and highly compatible with various sources of cell line-derived xenografts (CDXs) and patient-derived xenografts (PDXs).
    BRGSF mice lack mature T, B and NK cells. The replacement of Sirpa gene from BALB/c background by its allele from NOD background (SirpaNOD) markedly suppressed the phagocytic function of murine macrophages, and this model is highly compatible with various sources of cell line-derived xenografts (CDXs) and patient-derived xenografts (PDXs). Thus, BRGSF mice are suitable for solid tumor and hematoma research.
  • ● Effective differentiation of human myeloid cell lines (HMCs), and long-lasting reconstituted human cells - making BRGSF-HIS mouse a suitable model for long-term studies.

    BRGSF-HIS mice are reconstructed from human CD34+ hematopoietic stem cells (HSCs) transplantation, which possesses all of the major human hematopoietic cell subsets, such as T cells (including CD4+ Treg cells), B cells, NK cells, and the myeloid compartment including classical dendritic cells (cDCs), plasmacytoid cells (pDCs) and monocytes/macrophages. Flt3-L treatment can promote the development of human myeloid compartment (especially DCs), and the model can be used to study myeloid compartment development. Learn more>>

    BRGSF Mouse
The Application of BRGSF Mice
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CDX and PDX (e.g., solid tumor and hematoma research)
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Efficacy and safety assessment of cellular immunotherapy (e.g., CAR-T)
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Vaccine development (e.g., HIV)
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Myeloid compartment development (e.g., monocytes/macrophages)
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Construction of mouse models with reconstituted human immune systems (e.g. BRGSF-HIS)
Model Validation

● CDX model

Fig 1. Kinetics of tumor growth in mice bearing melanoma (A375) and breast cancer (MDA-MB-231) cell lines. A375 and MDA-MB-231 were inoculated into BALB/c nude, NOD scid and BRGSF mice by subcutaneous injection. The tumor volume was measured at different time points.

 

● huHSC immune system reconstitution

Fig 2. The reconstitution of human-derived cells in the peripheral blood of BRGSF mice, 10 weeks after transplantation of artificial hematopoietic stem cells. A) The proportion of human white blood cells (hCD45+) in the blood. B) Representative flow cytometry showing the reconstitution of the main immune cell population in hCD45+ cells (CD3+T cells, CD19+B cells, CD3-NKp46+NK cells and CD3-CD19-CD11c+HLA-DR+DC).

References

1. Simpson, J. A.; Brown, M. E. Making HIS Mice More Human - like. J. Leukoc. Biol. 2020, 107 (1), 9 - 10.

2. Lopez-Lastra, S.; Masse-Ranson, G.; Fiquet, O.; Darche, S.; Serafini, N.; Li, Y.; Dusséaux, M.; Strick-Marchand, H.; Di Santo, J. P. A Functional DC Cross Talk Promotes Human ILC Homeostasis in Humanized Mice. Blood Adv. 2017, 1 (10), 601–614.

3. Li, Y.; Mention, J.-J.; Court, N.; Masse-Ranson, G.; Toubert, A.; Spits, H.; Legrand, N.; Corcuff, E.; Strick-Marchand, H.; Di Santo, J. P. A Novel Flt3-Deficient HIS Mouse Model with Selective Enhancement of Human DC Development. Eur. J. Immunol. 2016, 46 (5), 1291–1299.

4. Legrand, N.; Huntington, N. D.; Nagasawa, M.; Bakker, A. Q.; Schotte, R.; Strick-Marchand, H.; de Geus, S. J.; Pouw, S. M.; Böhne, M.; Voordouw, A.; et al. Functional CD47/Signal Regulatory Protein Alpha (SIRPα) Interaction Is Required for Optimal Human T- and Natural Killer- (NK) Cell Homeostasis in Vivo. Proc. Natl. Acad. Sci. 2011, 108 (32), 13224–13229.

5. Valton J, Guyot V, Boldajipour B, et al. A Versatile Safeguard for Chimeric Antigen Receptor T-Cell Immunotherapies. Scientific Reports. 2018, 8(1).

Mouse Model With Reconstituted Human Immune System

The BRGSF-HIS mouse possesses the most functional reconstituted human immune system currently available on the market. Indeed, this mouse provides a very practical and reliable research platform for evaluating targeted biological drugs related to the regulation of human immune function.

Mouse Model With Reconstituted Human Immune System
  • ● Effective differentiation of human myeloid cell lines (HMCs), and long-lasting reconstituted human cells - making BRGSF-HIS mouse a suitable model for long-term studies.

    BRGSF-HIS mice are reconstructed from human CD34+ hematopoietic stem cells (HSCs) transplantation, which possesses all of the major human hematopoietic cell subsets, such as T cells (including CD4+ Treg cells), B cells, NK cells, and the myeloid compartment including classical dendritic cells (cDCs), plasmacytoid cells (pDCs) and monocytes/macrophages. Flt3-L treatment can promote the development of human myeloid compartment (especially DCs), and the model can be used to study myeloid compartment development.

    BRGSF-HIS mouse
  • ● Does not affect the DNA double-strand break repair due to the absence of the PrkdcSCID mutation. It has high radiation tolerance and is suitable for research on diseases that require radiotherapy and the construction of HIS mice.
  • ● No symptoms of anemia - no induction of overexpressed human cytokines, and therefore macrophages differentiated from human hematopoietic stem cells (HSCs) will not be overstimulated to engulf murine red blood cells (RBCs).
The Application of BRGSF-HIS Mice
CDX and PDX (e.g., solid tumor and hematoma research)
CDX and PDX (e.g., solid tumor and hematoma research)
Vaccine development (e.g., HIV)
Vaccine development (e.g., HIV)
Myeloid compartment development (e.g., monocytes/macrophages)
Myeloid compartment development (e.g., monocytes/macrophages)
Efficacy assessment of antibody drugs (e.g., the combinations of therapeutic polyclonal or monoclonal antibodies)
Efficacy assessment of antibody drugs (e.g., the combinations of therapeutic polyclonal or monoclonal antibodies)
Infectiology (e.g., HIV, Dengue virus, Ebola virus, CMV, RSV, HTLV, EBV)
Infectiology (e.g., HIV, Dengue virus, Ebola virus, CMV, RSV, HTLV, EBV)
Autoimmune diseases (e.g., systemic lupus erythematosus (SLE), ankylosing spondylitis (AS), rheumatoid arthritis (RA), systemic vasculitis, autoimmune hemolytic anemia, etc.)
Autoimmune diseases (e.g., systemic lupus erythematosus (SLE), ankylosing spondylitis (AS), rheumatoid arthritis (RA), systemic vasculitis, autoimmune hemolytic anemia, etc.)
Model Validation

● BRGSF-HIS mouse myeloid cell detection

Figure 1. Distribution of human myeloid subsets in BRGSF mice and effect of Flt3L on their development.

Fig 1. Distribution of human myeloid subsets in BRGSF mice and effect of Flt3L on their development. Representative flow cytometry immunophenotypic analysis of hCD45+HLA−DR+CD19CD3CD56cells from bone marrow (A) and spleen (C) of an Flt3L-treated mouse and a PBS-treated littermate engrafted with the same CD34+ HSC donor in BRGSF mice. Comparison of frequencies within the human CD45+cells and total number of the 4 myeloid subsets (CD14+monocytes, CD123+pDCs, CD141+cDCs, and CD1c+cDCs) with or without Flt3L treatment in bone marrow (B) and spleen (D).

References

1. Labarthe L, Henriquez S, Lambotte O, Di Santo JP, Le Grand R, Pflumio F, Arcangeli ML, Legrand N, Bourgeois C.Frontline Science: Exhaustion and senescence marker profiles on human T cells in BRGSF-A2 humanized mice resemble those in human samples.J Leukoc Biol. 2019 Aug 4.

2. Fournier N, Jacque E, Fontayne A, Derache D, Dupont G, Verhaeghe L, Baptista L, Dehenne A, Dezetter AS, Terrier A, Longue A, Pochet-Beghin V, Beghin C, Chtourou S, de Romeuf C.Improved in vitro and in vivo activity against CD303-expressing targets of the chimeric 122A2 antibody selected for specific glycosylation pattern.MAbs. 2018 May/Jun.

3. Masse-Ranson G, Mouquet H, Di Santo JP.A Versatile Safeguard for Chimeric Antigen Receptor T-Cell Immunotherapies.Curr Opin HIV AIDS. 2018 Mar.