BRGSF-A2-HIS Mouse Model

Immunodeficient mouse

Design of the BRGSF-A2-HIS mouse

The BRGSF-A2 model is generated by inserting a human leukocyte antigen serotype A2 (HLA-A2) class I transgene in the genome of BRGSF (Balb/c Rag2tm1Fwa IL2rγtm1Cgn SirpαNOD Flk2tm1Irl) mice. These mice are subsequently used as recipients to reconstitute a functional human immune system (HIS) to create BRGSF-A2-HIS mouse models.

Applications

The presence of HLA molecules on BRGSF-A2-HIS thymic epithelial cells hinders T cell cross-reactivity, making this model an invaluable tool to study:

  • Human cytotoxic T lymphocyte responses against human infectious diseases and malignancies
  • Preclinical efficacy of immunotherapies
  • Mechanisms regulating the expression of senescence biomarkers
 

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BRGSF-A2-HIS features

The BRGSF-A2-HIS mouse model possesses all of the major human hematopoietic cell subsets, such as B cells, T cells (including CD4+ Treg cells), NK cells, and the myeloid compartment including dendritic cells (DCs), plasmacytoid dendritic cells (pDCs) and monocytes/macrophages.

 

BRGSF-A2-HIS mouse model

  • Highly permissive to patient-derived xenografts (PDXs) and cell line engraftment by virtue of the SIRPαNOD allele expression
  • Suitable to assess the effects of radiation treatment in vivo due to the absence of the SCID mutation on a BALB/c background
  • A powerful tool for complement-dependent cytotoxicity (CDC) studies because of the presence of a functional murine complement system
  • A robust model to study T cell responsiveness to infection- or tumor-associated antigens in the context of the human MHC molecules

BRGSF-A2-HIS validation*

BRGSF-A2-HIS model validation 1

BRGSF-A2-HIS mice display a strongly humanized expression profile in blood and lymphoid tissues

Representative dot plots showing the relative proportion of murine and human CD45 (mCD45 and hCD45, respectively) cells in peripheral blood mononuclear cells (PBMC), splenocytes (SP), and bone marrow (BM) cells of 16-19-week-old BRGSF-A2-HIS mice.

BRGSF-A2-HIS model validation 2

Similar distributions of naive, memory and effector T cells in blood samples of BRGSF-A2-HIS mice and human healthy donors

In the graphs are reported the frequency of naive (white bars), memory (gray bars) and effector (black bars) T cells in the blood of BRGSF-A2-HIS mice (HIS) and healthy donors (HD).

BRGSF-A2-HIS model validation 3

BRGSF-A2-HIS mice recapitulate human senescence and exhaustion profiles

Frequency of CD57+ (A), KLRG1+ (B), PD-1+ (C) and TIGIT+ (D) cells among naive (white bars), memory (gray bars), and effector (black bars) human CD4+ and human CD8+ T cell subsets in peripheral blood mononuclear cells (PBMC), splenocytes (SP), and bone marrow (BM) preparations of BRGSF-A2-HIS mice (HIS) and healthy donors (HD).

* For more validation data please refer to Labarthe L, et al. Exhaustion and senescence marker profiles on human T cells in BRGSF-A2 humanized mice resemble those in human samples. J Leukoc Biol. 2019 Aug., or  contact us.

Ready to be shipped to your lab

  • Cohorts available upon request
  • Studies can be carried out at your site or at your favorite CRO
  • VAF Elite/SOPF certification and worldwide delivery by professional breeders
  • Models provided with FTO on patent-protected technologies used for model generation