PMID:14707083

Citation	Webb, DC, Matthaei, KI, Cai, Y, McKenzie, AN and Foster, PS (2004) Polymorphisms in IL-4R alpha correlate with airways hyperreactivity, eosinophilia, and Ym protein expression in allergic IL-13-/- mice. J. Immunol. 172:1092-8
Abstract	The development of airways hyperreactivity in allergic IL-13(-/-) mice is controversial and appears to correlate with the number of times that the original 129 x C57BL/6 founder strain has been crossed to the BALB/c background. In this investigation, we compared allergic responses in founder IL-13(-/-) mice crossed for either 5 (N5) or 10 (N10) generations to BALB/c mice. Whereas allergic N5 IL-13(-/-) mice developed airways hyperreactivity, tissue eosinophilia, elevated IgE, and pulmonary expression of Ym proteins, these processes were attenuated in N5 IL-13(-/-) mice treated with an IL-4-neutralizing Ab, and in N10 IL-13(-/-) mice. These data showed that IL-4 was more effective in regulating allergic responses in N5 IL-13(-/-) mice than in N10 IL-13(-/-) mice. To elucidate the mechanism associated with these observations, we show by restriction and sequence analysis that N5 IL-13(-/-) mice express the C57BL/6 form of IL-4Ralpha and N10 IL-13(-/-) mice express the BALB/c form. Despite the near identical predicted molecular mass of these isoforms, IL-4Ralpha from N5 IL-13(-/-) mice migrates with a slower electrophoretic mobility than IL-4Ralpha from N10 IL-13(-/-) mice, suggesting more extensive posttranslational modification of the N5 form. The Thre(49)Ile polymorphism in the extracellular domain of BALB/c IL-4Ralpha has been demonstrated to disrupt N-linked glycosylation of Asn(47) and increase the dissociation rate of the IL-4Ralpha/IL-4 interaction. Collectively, these data show that polymorphisms in IL-4Ralpha, which have been shown to affect the interaction with IL-4, correlate with the ability of IL-4 to regulate allergic responses in IL-13(-/-) mice.
Links	PubMed
Keywords	Adipokines; Amino Acid Sequence; Animals; Bronchial Hyperreactivity/genetics; Bronchial Hyperreactivity/immunology; CD4-Positive T-Lymphocytes/chemistry; CD4-Positive T-Lymphocytes/immunology; CD4-Positive T-Lymphocytes/metabolism; Cell Division/genetics; Cell Division/immunology; Cytokines/biosynthesis; Electrophoresis, Polyacrylamide Gel; Eosinophilia/genetics; Eosinophilia/immunology; Female; Glycoproteins/chemistry; Immunoglobulin E/biosynthesis; Interleukin-13/deficiency; Interleukin-13/genetics; Lectins/biosynthesis; Lectins/chemistry; Lectins/genetics; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Molecular Sequence Data; Polymorphism, Genetic/immunology; Protein Isoforms/biosynthesis; Protein Isoforms/chemistry; Protein Isoforms/genetics; Protein Isoforms/physiology; Protein Subunits/biosynthesis; Protein Subunits/chemistry; Protein Subunits/genetics; Protein Subunits/physiology; Receptors, Interleukin-4/biosynthesis; Receptors, Interleukin-4/chemistry; Receptors, Interleukin-4/genetics; Receptors, Interleukin-4/physiology; Respiratory Hypersensitivity/genetics; Respiratory Hypersensitivity/immunology; beta-N-Acetylhexosaminidases/biosynthesis; beta-N-Acetylhexosaminidases/chemistry; beta-N-Acetylhexosaminidases/genetics
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