title: An interleukin-33 gene polymorphism is a modifier for eosinophilia in rats.
abstract: In previous studies, we identified a loss-of-function mutation in the Cyba gene as the primary cause of hereditary eosinophilia in the Matsumoto Eosinophilia Shinshu (MES) rat strain. We also identified a modifier locus for eosinophilia named eos3 in rats. In this study, we examined the interleukin-33 (Il33) gene as a candidate for the eos3 and found a missense nucleotide substitution in the gene, which resulted in a G171S amino-acid substitution in the IL-33 protein. Recombinant IL-33 isoform with the G171S substitution had approximately 50% of activity of normal isoform in NF-κB-dependent reporter assay, and reduced bioactivity (∼65% of normal) to provoke eosinophilia when injected into mice. In a genetic association study using (ACI × MES) × MES backcross rats, we found that the effects of polymorphic Il33 alleles on blood eosinophil level were manifested only in rats with loss of Cyba function. In these rats, the blood eosinophil level was significantly lower (∼50%) in heterozygotes for the ACI allele of Il33 compared with homozygotes for the MES allele. Oddly, however, eosinophilic MES rats had blood IL-33 content below the detectable limits. These results suggest that the Il33 gene polymorphism could be a modifier of eosinophilia in rats.
authors: Department of Aging Biology, Institute of Pathogenesis and Disease Prevention, Shinshu University Graduate School of Medicine, Matsumoto, Japan.
authors: H
authors: H
authors: Luo
authors: K
authors: K
authors: Higuchi
authors: K
authors: K
authors: Matsumoto
authors: M
authors: M
authors: Mori
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D053148:Caspase 3 / Q000378:metabolism; D003573:Cytochrome b Group / Q000235:genetics; D004802:Eosinophilia / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D000067596:Interleukin-33; D007378:Interleukins / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D020125:Mutation, Missense; D019255:NADPH Oxidases / Q000235:genetics; D011110:Polymorphism, Genetic; D051381:Rats; D011912:Rats, Inbred ACI; D011922:Rats, Mutant Strains; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000235:genetics
chemical_list: D003573:Cytochrome b Group; C553108:Il33 protein, rat; D000067596:Interleukin-33; D007378:Interleukins; D019255:NADPH Oxidases; C515768:Cyba protein, rat; D053148:Caspase 3