BRGSF-A2-HIS mouse model | humanized for immune system

BRGSF-A2-HIS 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.

Highly permissive to human xenograft, including primary or established tumor cells (CDX or PDXs) by virtue of the SIRPα^NOD allele expression
Lifespan after humanization similar to that of the wild-type mouse _⇨ supports long-term engraftment studies
Robustness to traveling (stable immune system)
Suitable to assess the effects of radiation treatment in vivo due to the absence of the SCID mutation on a BALB/c background
A complete, functional complement system makes this a powerful tool for complement-dependent cytotoxicity (CDC) studies
A robust model to study T-cell responsiveness to infection- or tumor-associated antigens in the context of the human MHC molecules

Validation

genO‑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 genO‑BRGSF‑A2‑HIS mice.
Similar distributions of naive, memory and effector T cells in blood samples of genO‑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 genO‑BRGSF‑A2‑HIS mice (HIS) and healthy donors (HD).
genO‑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 genO‑BRGSF‑A2‑HIS mice (HIS) and healthy donors (HD).