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

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 SIRPαNOD 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

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