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.

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) Functional data on double-humanized IgE/FcεRI model: Inhibition of mast cell degranulation by anti-IgE monoclonal Ab.

Figure 3 - double humanized IgE-FcepsilonR1 mouse

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