Chimeric IgE/FcεR1 complex with 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]
The humanized IgE/FcεR1 mouse model has been successfully used to screen for innovative therapeutics for allergy(e.g., allergic rhinitis, atopic dermatitis, food allergies, chronic urticaria), asthma and other IgE-mediated diseases (Eosinophilic esophagitis and inflammatory bowel disease)s, and improve the translatability and predictability of IgE-mediated reactions.
Figure 1. Expression of hFcεR1 in 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)
Figure 2. Analysis of human FcεR1 and human IgE expression in double humanized IgE/FcεR1 mouse cells. a) Expression of hFcεR1-α chain from bone marrow-derived mast cells cultured in presence of murine IL3, SCF, and IL6 for 8 weeks. b) Human IgE in serum of mice sensitized and challenged with ovalbumin. (black column: treated; white column: untreated)
Figure 3. The functional data of the humanized IgE/FcεR1 mouse model. (Left) After binding to hFcεR1, IgE triggers the degranulation of mast cells. (Right) Mast cells respond to hFcεR1, but do not respond to mFcεR1 cross-linking (XL).
Conclusion: Mast cells from the humanized model bind human IgE and degranulate upon cross-linking. This is specific and not restricted to given antigen. This set of data validates the functionality of the IgE high-affinity receptor. It binds human IgE and triggers degranulation upon cross-linking.
Figure 4. Functional data on double humanized IgE/FcεRI model: Inhibition of mast cell degranulation by anti-IgE monoclonal Ab. Mast cells were sensitized overnight with human IgE in presence of indicated biologics. The cells were washed and stimulated with anti-IgE. β-hexosaminidase activity in cell supernatant was determined as a percentage of total β-hexosaminidase activity in cell lysates.
Conclusion: Anti-IgE Ab, but not the isotype control, suppresses hFcεR1-mediated degranulation in a dose-dependent manner.
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|Category||Strain Name||Background||Order Amount
Allergy Humanized Mice
|hIgE + FcεR1||BALB/c||1~50||$619|
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With more than 15 years’ experience in genetic engineering, Cyagen offers a complete range of products and services to support the advancement of human disease research. Cyagen is committed to enabling the development of therapeutics for human diseases by providing one-stop research solutions – from custom rodent model generation and breeding, through therapeutic viral packaging and injection, and phenotype analysis to study disease mechanisms, target validation, drug screening and more.
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