“Among several commercial services who have claimed to be specialized to generate mouse models with genetic modifications, I recognize that Cyagen is one of the best. We are looking forward to having more cooperation with them.”Korea Brain Research Institute (KBRI)
영업일 기준 1-2일 내에 답변해 드리겠습니다.
Strain Background: C57BL/6N
Research & Application:
The humanized IgE/FcεR1 mouse model has been successfully used to screen for innovative therapeutics for allergy, asthma and other IgE-mediated diseases (Eosinophilic esophagitis and inflammatory bowel disease).
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.
Figure 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. b) Human IgE in serum of mice sensitized and challenged with ovalbumin. (black column: treated; white column: untreated)
Figure 2. Functional data on double humanized IgE/FcεR1 model: Induction of mast cell degranulation by anti-IgE Ab. Mast 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.
Figure 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.
Figure 4. Expression of hFcεR1 in humanized IgE/FcεR1 mouse cells. (Left) The expression of hFcεR1α chain was detected on mast cells (BMMCs) derived from mouse bone marrow stimulated by IL-3, stem cell factor (SCF) and IL-6 (8 weeks of treatment). (Right) hFcεR1 mice were injected intravenously with eotaxin (2.4nmol/kg), and hFcεR1 expression was detected in peripheral blood eosinophils.
Figure 5. 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).