Humanized IgE/FcεR1 Mouse Model to Study IgE-Mediated Diseases

Humanized IgE/FcεR1 Mouse Models

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.

hIgE/hFcεR1 model features

  • Expression of human IgE and human FcεR1 without expression of their murine counterparts
  • Human pattern of expression of hFcεR1 thanks to the use of the human promotor
  • Suitable model for passive systemic anaphylaxis and evaluation of anti-hIgE compounds
 

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hIgE/hFcεR1 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.

A) Expression of hFcεR1-α chain from bone marrow-derived mast cells cultured in presence of murine IL3, SCF, and IL6 for 8 weeks.

Figure 1a - double humanized IgE-FcepsilonR1 mouse

B) Human IgE in serum of mice sensitized and challenged with ovalbumin. (black column: treated; white column: untreated)

Figure 1b - double humanized IgE-FcepsilonR1 mouse

Fig. 2) Functional data on double-humanized IgE/FcεR1 model: Induction of mast cell degranulation by anti-IgE Ab.

Figure 2 - double humanized IgE-FcepsilonR1 mouseMast cells were sensitized with human IgE overnight to load hFcεR1 receptors and degranulation was stimulated by cross-linking loaded receptors with anti-hIgE.

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) 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.

Figure 3a - double humanized IgE-FcepsilonR1 mouse

Figure 3b - double humanized IgE-FcepsilonR1 mouse

* For more validation data please contact us.

 

Ready to be shipped to your lab

  • Cohorts available upon request
  • Studies can be carried out at your site or at your favorite CRO
  • SOPF certification and worldwide delivery by professional breeders
  • Models provided with FTO on patent-protected technologies used for model generation