Mice homozygous for this Il4ra^F709 (IL-4Rα Y709F) polymorphic allele are viable and fertile. The mutation introduces a tyrosine to phenylalanine amino acid substitution at codon 709 (Y709F) within the canonical immunoreceptor tyrosine-based inhibitory motif (ITIM) sequence near the carboxyl-terminus of the protein. This Y709F polymorphism prevents ITIM phosphorylation and inhibit the binding of regulatory phosphatases (including Src homology 2 domain-containing protein tyrosine phosphatase 1 [SHP-1]), resulting in enhanced receptor signaling. Allele-specific PCR verifies the Y709 to F709 codon substitution. Homozygous mice exhibit enhanced phosphorylation of signal transducer and activator of transcription 6 (STAT6) in B cells following IL-4 treatment, and increased serum concentrations of total IgE and ovalbumin (OVA)-specific IgE after immunization with OVA/alum. Il4ra^F709/F709 mice have increased allergic airway inflammation (peribronchial and perivascular inflammation, goblet cells and eosinophil accumulation) and airway hyperresponsiveness in response to allergen sensitization and challenge.

Both untreated and OVA-challenged homozygous mice exhibit upregulated expression of a number of STAT6-responsive genes involved in allergic airway inflammation. The Y709F substitution results in increased IL-4 production after Th2 polarization (Th2 bias) and enhanced alternative macrophage activiation by IL-13 in vivo.
The Il4ra^F709/F709 mice are highly susceptible to oral sensitization to OVA, even in the absence of adjuvants, and sensitized mice respond to oral challenge with anaphylaxis. These Il4ra^F709 mutant mice may be useful in immunological studies of mitogenic signal transduction, specifically antigen-specific antibody responses, allergic airway inflammation, atopy, asthma, and food allergy research.