Anaphylaxis mediated through a humanized high affinity IgE receptor

Mast cells and basophils, which are activated by Igf and allergens through the high affinity IgE receptor (FctRI), play a prominent role in anaphylaxis in the mouse. Mice deficient in this receptor become resistant to passive anaphylaxis. As a first step

in developing an in vivo model that more closely mimics the IgE-mediated responses in man, we used a combination of

transgenic and embryonic stem cell technology to generate a mouse line in which the murine FceRl a-chain has been replaced

with its human homologue. We demonstrate here that these mice express a tetrameric high affinity IgE receptor, in which the

human a-chain associates with the murine p- and y-chains, and that upon triggering with relevant Ag, this receptor mediates

the initiation of the expected intracellular events. In addition, we show that the human a-chain restores an anaphylactic

response to the nonresponsive a-deficient parental mouse line. This “humanized” mouse represents a potentially important

model system, not only for studying the role of IgE in human immune responses, but also for testing potential therapeutic

reagents that can interfere with responses mediated through the human FceRI receptor.

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