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Genetics of atopy in a mouse model: polymorphism of the IL-5 receptor α chain

Item Type:Article
Title:Genetics of atopy in a mouse model: polymorphism of the IL-5 receptor α chain
Creators Name:Daser, A. and Koetz, K. and Batjer, N. and Jung, M. and Rueschendorf, F. and Goltz, M. and Ellerbrok, H. and Renz, H. and Walter, J. and Paulsen, M.
Abstract:To study the genetics of atopy systematically we established a mouse model that provides the general pheontype of atopy: the early response characteristic of IgE-dependent eczema or atopic dermatitits, and the diagnostic test of atopy, the skin-prick test. Using an immediate cutaneous hypersensitivity test (ICHS) against birch pollen extract we could classify A/J and C57BL/6 (B6) inbred mouse strains respectively as high responder and low responders. The F1 hybrids were found to be high responders with incomplete penetrance. Backcrossing F1 mice to low responder B6 strain yielded three classes of responders, high, intermediate and low. A genomwide microsatellite screen of the backcross progeny disclosed suggestive linkage to a microsatellite marker on chromosome 6 close zo the locus of te IL-receptor {alpha} chain. Its allelic variation in A/J and B6 strains was investigated and two major differences were detected. Firstly, a nucleotide exchange in the 5' untranslated region of B6 mRNA resulted in increased transcription/translation of a reporter construct. Higher expression of the receptor on the cell surface would be expected to favor an allergic immune response. Secondly, the two alleles are differentially spliced so as to yield two soluble isoforms in A/J mice versus one in B6 mice. Higher expression of soluble IL-5R would be expected to reduce the level of allergy through capture of IL-5. Thus both findings conform to the expectation based on susceptibility to atopy and thus indentify the IL-5R {alpha} chain as a likely contributor to the genetics of atopy.
Keywords:Atopy, Genetics, Polymorphism, Interleukin-5 Receptor, Alternative Splicing, Animals, Mice
Source:Immunogenetics
ISSN:0093-7711
Publisher:Springer (Germany)
Volume:51
Number:8
Page Range:632-638
Date:July 2000
Official Publication:https://doi.org/10.1007/s002510000206
PubMed:View item in PubMed

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