Humanized IgE / FcepsilonR1 Mouse Model to Study IgE-Mediated Diseases
Applications: Allergy, autoimmune disease, and inflammation
The humanized IgE/FcεR1 mouse model has been successfully used to screen for innovative therapeutics for allergy, asthma and other IgE-mediated diseases.
Model features:
- Human IgE immunoglobulin and no mouse IgE immunoglobulin (Fig. 1B)
- Human FcεRI receptor and no mouse FcεRI receptor (Fig. 1A)
- hFcεRI receptor is expressed under the control of the human promoter to mimic the human pattern of expression
Model validation
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.
Fig. 1) Analysis of human FcεR1 and human IgE expression in double-humanized IgE/FcεR1 mouse cells. |
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A) Expression of hFcεR1-α chain from bone marrow-derived mast cells cultured in presence of murine IL3, SCF, and IL6 for 8 weeks.
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B) Human IgE in serum of mice sensitized and challenged with ovalbumin. (black column: treated; white column: untreated)
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Fig. 2) Functional data on double-humanized IgE/FcεR1 model: Induction of mast cell degranulation by anti-IgE Ab. |
β-hexosaminidase activity in cell supernatant was determined as a percentage of total β-hexosaminidase activity in cell lysates. 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. |
Fig. 3) 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. |
Ready to be shipped to your lab
- Available onto BALB/c genetic background
- Health-certified prior to delivery: SOPF (Specific and Opportunistic Pathogen-Free)
- Worldwide delivery using logistic networks of professional breeders
Access conditions
- Freedom to operate for basic and pharmaceutical research
- Generated data are the exclusive property of the customer and royalty-free
- The model is available through in-licensing (flat annual fee, depending on company size)
- On-demand production of cohorts by contract breeding