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An interleukin-33 gene polymorphism is a modifier for eosinophilia in rats
Luo, H
Higuchi, K
Matsumoto, K
Mori, M
eosinophil
gene polymorphism
interleukin-33
modifier
rat
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-kappa B-dependent reporter assay, and reduced bioactivity (similar to 65% of normal) to provoke eosinophilia when injected into mice. In a genetic association study using (ACI x MES) x 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 (similar to 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. Genes and Immunity (2013) 14, 192-197; doi:10.1038/gene.2013.7; published online 28 February 2013
Article
GENES AND IMMUNITY. 14(3):192-197 (2013)
NATURE PUBLISHING GROUP
2013
eng
journal article
AM
http://hdl.handle.net/10091/17263
https://soar-ir.repo.nii.ac.jp/records/3776
https://pubmed.ncbi.nlm.nih.gov/23446743
23446743
https://doi.org/10.1038/gene.2013.7
10.1038/gene.2013.7
1466-4879
AA11474931
GENES AND IMMUNITY
14
3
192
197
https://soar-ir.repo.nii.ac.jp/record/3776/files/interleukin-33_gene_polymorphism_modifier_eosinophilia_rats.pdf
application/pdf
520.7 kB
2015-09-24