Transgenic mice expressing the human high-affinity immunoglobulin (Ig) E receptor α chain respond to human IgE in mast cell degranulation and in allergic reactions

Wai Ping Fung-Leung, Jean De Sousa-Hitzler, Armana Ishaque, Lubing Zhou, Jesse Pang, Karen Ngo, Julie A. Panakos, Erika Chourmouzis, Fu-Tong Liu, Catherine Y. Lau

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Abstract

The high-affinity receptor for immunoglobulin (Ig) E (FcεRI) on mast cells and basophils plays a key role in IgE-mediated allergies FcεRI is composed of one α, and β, and two γ chains, which are all required for cell surface expression of FcεRI, but only the α chain is involved in the binding to IgE FcεRI-IgE interaction highly species specific, and rodent FcεRI does not bind human IgE. To obtain a 'humanized' animal model that responds to human IgE in allergic reactions, transgenic mice expressing the human FcεRI α chain were generated. The human FcεRI α chain gene with a 1.3-kb promoter region as a transgenic was found to be sufficient for mast cell-specific transcription. Cell surface expression of the human FcεRI α chain was indicated by the specific binding of human IgE to mast cells from transgenic mice in flow cytometric analyses. Expression of the transgenic FcεRI on bone marrow-derived mast cells was 4.7 x 104/cell, and the human IgE-binding affinity was K(d) = 6.4 nM in receptor-binding studies using 125I-IgE. The transgenic human FcεRI α chain was complexed with the mouse β and γ chains in immunoprecipitation studies. Cross-linking of the transgenic FcεRI with human IgE and antigens led to mast cell activation as indicated by enhanced tyrosine phosphorylation of the FcεRI β and γ chains and other cellular proteins. Mast cell degranulation in transgenic mice could be triggered by human IgE and antigens, as demonstrated by β-hexosaminidase release in vitro and passive cutaneous anaphylaxis in vivo. The results demonstrate that the human FcεRI α chain alone not only confers the specificity in human IgE binding, but also can reconstitute a functional receptor by coupling with the mouse β and γ chains to trigger mast cell activation and degranulation in a whole animal system. These transgenic mice 'humanized' in IgE-mediated allergens may be valuable for development of therapeutic agents that target the binding of IgE to its receptor.

Original languageEnglish (US)
Pages (from-to)49-56
Number of pages8
JournalJournal of Experimental Medicine
Volume183
Issue number1
DOIs
StatePublished - Jan 1 1996

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ASJC Scopus subject areas

  • Immunology

Cite this

Fung-Leung, W. P., De Sousa-Hitzler, J., Ishaque, A., Zhou, L., Pang, J., Ngo, K., Panakos, J. A., Chourmouzis, E., Liu, F-T., & Lau, C. Y. (1996). Transgenic mice expressing the human high-affinity immunoglobulin (Ig) E receptor α chain respond to human IgE in mast cell degranulation and in allergic reactions. Journal of Experimental Medicine, 183(1), 49-56. https://doi.org/10.1084/jem.183.1.49