BRGS A2DR2-HIS Humanized Mouse
Model characteristics
Type:
Inbred transgenic mouse, GEMM
Strain name:
C-Rag2tm1-Il2rgtm1-SirpaNOD- Tg(HLA-A*02- HHD)-Tg(HLA-DR2)/Rj
Origin:
Pasteur institute, 2022
Colour and related genotype:
Albino mouse
Breeding:
CD34 from blood cord.
Treatment: Irradiation
Description of our model and application areas
Humanized CD34+ mice are the epitome of mice models in terms of surrogate models for humans. Application field ranges from immunology, oncology, infectious diseases and more. This innovative approach bridges the gap between <em>in vitro</em> studies and clinical trials, providing a platform for more accurate and translational investigations in immunology and regenerative medicine.
In that frame, BRGS A2DR2-HIS mice go one step further in comparison to other humanized models by providing accelerated thymopoiesis as well as improved T-cell responses
The BRGS A2DR2 mouse model:
The BRGS A2DR2 strain is a highly immunodeficient inbred model characterized by knockout mutations in the <em>Il2rg</em> and <em>Rag2</em> genes, with a NOD background gene. The <em>Rag2</em> knockout inhibits the formation of B and T cell receptors, leading to the absence of T and B lymphocytes. The <em>Il2rg</em> knockout affects the gamma c chain crucial for immune cell differentiation, resulting in the absence of T, B, and NK cells. The combination of these mutations induces severe immunodeficiency.
Additionally, the strain carries the NOD variant of the <em>Sirpa</em> gene, reducing phagocytosis of transplanted human cells. Finally, this strain expresses human HLA-A*02 and HLA-DR2 transgenes.
Main application and research fields
Humanization process
The process of humanization involves injecting cord blood-derived human CD34+ cells into mice after inducing myeloablation. This technique allows for the development of a functional and multi-lineage human immune system within the murine host. The use of cord blood as a source of hematopoietic stem cells offers advantages such as accessibility, ethical considerations, and the potential for diverse immune cell populations.
The presence of HLA-A*02 and HLA-DR2 transgenes allows for a more rapid emergence of T cells in the hosts’ circulation, indicating a potentially more efficient development of human T cells in the mouse thymus following the engraftment of human CD34+ stem cells. The acceleration of CD4+ and CD8+ T cell development in BRGS A2DR2-HIS mice leads to a more balanced composition of B and T cell compartments in peripheral lymphoid organs. The presence of human HLA transgenes enhances both B- and T-cell functions, resulting in elevated levels of class switched Ig, increased percentages of polyfunctional T cells, and clear indications of antigen-specific T-cell responses post-immunization.
Proper engraftment of the immune system engraftment is assessed between weeks 12-14 by ensuring that over 20% of human CD45+ cells are present in the peripheral blood.
BRGS A2DR2-HIS mice stand as a versatile model, resistant to genotoxic agents and perfect for any applications related to T-cell therapies (TCR redirected T-cells, vaccines…).
Services
The scientific team at Janvier Labs is always available to assist you in optimizing the utilization of our BRGS-HIS mice. Reach out to us to explore how we can contribute to the success of your experiments.
- Typically, our mice, along with a comprehensive report on human system engraftment and sanitary status, are shipped to customers around week 16 post-engraftment. But we can offer to liberate the animals sooner to accommodate your needs.
- We recommend engrafting with CD34+ cells from HLA-A*02:01 donors to maximize the pertinence of the BRGS A2DR2-HIS models but can accommodate additional requests.
- If specific percentages of the lymphoid and myeloid compartments are desired to tailor the use of NRG-HIS mice to your research needs, we can selectively choose animals that best suit your requirements.
Flow cytometry analysis, spleen
Kinetics of human cell reconstitution in the blood of BRGS versus BRGS A2DR2-HIS mice.
Antigen-specific HIV responses in BRGS versus BRGS A2DR2 mice.
Quality control of the humanization rate
Quality control allows to measure the relative humanization rate of humanized mice in the peripheral blood. The standardization of quality control is performed by flow cytometry of the different human populations: hematopoietic, lymphoid and myeloid. Each BRGS A2DR2-HIS is tested and analyzed before sending and use. BRGS A2DR2-HIS mice are produced with SOPF status. Each batch provided is supplied with a list showing the animal repartition according to the different CD34+ donors.
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