Humanized IgE/FcεR1 mouse model
Use the hIgE/hFcεR1 mouse model to successfully screen for innovative therapeutics for allergy, asthma and other IgE-mediated diseases.
A major limit for in vivo studies is the different cellular distribution of the IgE high-affinity receptor. In mice, the IgE high-affinity receptor is not expressed on monocytes/DCs, Langerhans cells, or eosinophils whereas it is in humans.
The model enables the production of a fully human IgE-FcεRI complex combined with a human-like expression of a FcεRI receptor.
hIgE/hFcεR1 model features
- Human-like cellular distribution (i.e., mast cells, basophils, monocytes/DCs, Langerhans cells, and eosinophils) of the FcεR1 receptor due to the presence of a minimal human promoter that drives its expression
- Physiological regulation and expression of the chimeric IgE/FcεR1 complex [humanized IgE/FcεR1 interactive domains (i.e., IgE Fc region and FcεR1 α-chain), and murine IgE Fab region and FcεR1 β- and γ-chains]
Validation
Analysis of human FcεR1 and human IgE expression in double-humanized IgE/FcεR1 mouse cells.
Left panel: Expression of hFcεR1 α-chain from bone marrow-derived cultured mast cells (BMMCs) in presence of murine IL-3, stem cell factor (SCF) and IL-6 (8 weeks treatment).
Right panel: Expression of hFcεR1 on murine eosinophils in peripheral blood upon intravenous injection of eotaxin (2.4 nmol/kg).
Functional data on double-humanized IgE/FcεR1 mouse model
- Mast cells sensitization OVN with hIgE in the presence mAbs
- Stimulation with anti-hIgE
- β-hexosaminidase activity in cell supernatant determined as a percentage of total enzyme activity in cell lysates
Passive systemic anaphylaxis is inducible in hIgE/hFcER1 mouse model and inhibited by a specific anti-hIgE treatment
The model has been successfully used by Ambiotis, a Contract Research Organization (CRO) providing inflammation assays and lipid analytical services.
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Humanized IgE/FcεR1 mouse model
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