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BRGSF-A2-HIS
Humanized mice (HIS/human immune system)

BRGSF-A2-HIS mouse model

BRGSF-A2-HIS mice possess the most functional reconstituted human immune system. HLA molecules on thymic epithelial cells hinder T-cell cross-reactivity.

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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.

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  • 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

Related resources and publications

TFRC

FX-deficiency

muscle-eye-brain disease (MEB)

TME

primary immunodeficiency (PID)

Oncology

Pharmacology

Neuroscience

Metabolism

Inflammation

Immunology

Respiration

Cardiovascular

Ophthalmology

Nephrology

Musculoskeletal

Hematology

Epigenetics

Development

Endocrinology

Dermatology

Humanization

Rosa26

TET system

Hprt

CreERt2

FLEx

innate immunity

Transgenesis

infection

vision

immune response

dementia

central nervous system (CNS)

taste

transplantation

autoimmunity

thermoregulation

sugar homeostasis

stress

skelet

pulmonary research

nutrition

pain research

muscle research

locomotion

memory

hearing

fat homeostatsis

tissue research

epigentic modification

drugs

cancer research

cell research

behavior

aging

stem cell research

reproductive research

lymphatic system

learning

heart research

gut research

genetic research

exercise

bone research

embryonic development

dental research

blood research

von Willebrand disease (VWD)

X-linked adrenoleukodystrophy (X-ADL)

Vanishing White Matter (VWM) disease

type 2 diabetes (T2D)

ulcerative colitis (UC)

type 1 diabetes (T1D)

thrombosis

thrombocytopenia

systemic lupus erythematosus (SLE)

tauopathy

stenosis

steatohepatitis

spinocerebellar ataxia type 2 (SCA2)

small cell lung cancer

SHORT syndrome

sepsis

schizophrenia

Senescence-associated secretory phenotype (SASP)

seizure

sarcoidosis

rhesus-deficiency syndrome

retinopathy

retinitis pigmentosa (RP)

retinal dystrophy disorder

pulmonary hypertension (PH)

primary sclerosing cholangitis (PSC)

postpartum depression (PPD)

pemphigus vulgaris

Parkinson's disease (PD)

papilloma

pancreatic cancer

Paget's disease

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Case studies
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Scientific Articles
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Homeostasis of monocytes and lung interstitial macrophages is regulated by collagen domain-binding receptor LAIR1 in vivo

Myeloid compartment in BRGSF-HIS

6 min read
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Jun 2022
Predictive in vivo evaluation of immunotherapy efficacy: tHIS is a reliable model

PDX in BRGSF-HIS

6 min read
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Nov 2021
Deciphering high-dose IL-2 toxicity in reconstituted HIS mice

Immunotherapy in BRGSF-HIS

6 min read
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Aug 2021
Myeloid and dendritic cells enhance therapeutics-induced cytokine release syndrome features in humanized BRGSF-HIS preclinical model

CRS in BRGSF-HIS

7 min read
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Feb 2024
Targeting myeloid cells in the tumor microenvironment in BRGSF-HIS mice

Myeloid compartment in BRGSF-HIS

7 min read
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Dec 2023
Assessing T-cell engagers efficacy in vivo: Versatility of BRGSF-HIS mice

Assess T-cell engager in BRGSF-HIS

3 min read
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Oct 2023
Expression of druggable myeloid targets in the BRGSF-HIS preclinical model

Myeloid compartment in BRGSF-HIS

3 min read
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Mar 2023
Functional human myeloid compartment in BRGSF-HIS preclinical model

Myeloid compartment in BRGSF-HIS

4 min read
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Nov 2022
Assessing T-cell engagers in vivo: How BRGSF-HIS mice can help

Assess T-cell engager in BRGSF-HIS

6 min read
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Jun 2022
Challenging the predictability of preclinical models for assessment of T-cell engagers

Assess T-cell engager in BRGSF-HIS

5 min read
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May 2022
Targeting tumor-associated myeloid cells: The new grail in immuno-oncology?

Myeloid compartment in immuno-oncology

3 min read
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Apr 2022
Immunotherapy efficacy assessment and metastases studies: tHIS model is highly permissive to engraftment

Engraftments in BRGSF-HIS

8 min read
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Nov 2021
Cytokine release syndrome (CRS)

Assess T-cell engager in BRGSF-HIS

5 min read
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Sep 2021
Tumor grafts in preclinical research: Models, models, overall, who is the fittest of them all?

Tumor-graft models

5 min read
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Aug 2021
Define “humanized”: two mouse models helping produce cancer immunotherapies

Humanized mouse models

4 min read
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Nov 2020
Part 3: BRGSF-HIS, a new human immune system mouse model for immuno-oncology studies

Immuno-oncolology models

6 min read
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Apr 2020
Part 1:  Toward a better effective preclinical model in immuno-oncology

Immuno-oncolology models

10 min read
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Jan 2020
VISTA checkpoint inhibition by pH-selective antibody SNS-101 with optimized safety and pharmacokinetic profiles enhances PD-1 response

Nat Commun

Apr 2024
Highlighted article
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Cell-depleting agents assessment in preclinical models

BRGSF-HIS & hFcγR to assess cell depletion

Nov 2023
Functional human myeloid cells in BRGSF-HIS humanized mice enable myeloid-directed therapy assessment

BRGSF-HIS for myeloid-directed therapy assessment

Apr 2023
CD3 humanized mouse models as validated tools to assess immune-related adverse events of T-cell engagers

CD3 and BRGSF-HIS to assess IrAEs

Nov 2022
Anti-VISTA agents profiling: complementarity of BRGSF-HIS and hVISTA Knock-in as preclinical models for immunotherapies

BRGSF-HIS & hVISTA for immunotherapies

Nov 2022
Translatable preclinical mouse models for assessment of T-cell engager-induced CRS

BRGSF-HIS & CD3ε in CRS

Apr 2022
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Compared to NOD-SCID and NSG, the BRGSF mouse represents the most adapted animal model to study and predict human immune responses in vivo.

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BRGSF-HIS mice possess the most functional reconstituted human immune system currently on the market and are highly relevant for translational research.

BRGSF-A2-HIS mouse model

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