Genetische Disposition von Immunglobulintitern nach Immunisierung mit Birkenpollen bei Mäusen

Atopische Erkrankungen, zu denen die atopische Dermatitis, die allergische Rhinokonjunktivitis und das Asthma bronchiale zählen, sind sowohl umweltbedingt als auch genetisch prädisponiert. Ziel dieser Studie war das Identifizieren von Genen bzw. Chromosomenabschnitten, die mit atopischen Phänotypen...

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Bibliographic Details
Main Author: Kölsch, Uwe
Contributors: Renz, Harald (Prof. Dr.) (Thesis advisor)
Format: Doctoral Thesis
Published: Philipps-Universität Marburg 2005
Online Access:PDF Full Text
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Atopic diseases like atopic dermatitis, allergic rhinoconjunctivitis and asthma bronchiale possess both environmental and genetic factors. The aim of this study was the identification of genes associated with atopic phenotypes. Therefore an animal model of allergic inflammation resulting from immunization with birch pollen was used. Delayed type hypersensitivity (type 1 allergic reaction according to Coombs and Gell) was measured (Gell et al., 1975) as well as birch pollen specific IgE-, IgG1- and IgG2a-titers and total IgE. Two inbred strains of mice were found developing different reactions in the delayed type hypersensitivity test. Offspring from these two inbred strains in the F1, F2 and F2-backcross generation and both parental strains were tested for the development of allergic reactions and allergen specific immunoglobuline titers were measured. From the immunoglobulin phenotype distribution in the offspring generation we concluded a codominant polygenic devolution. 160 markers with a mean distribution of 10,4 cM (1,4-25cM) were used for linkage analysis with immunoglobulin titers. On the long arm of Chromosome 17 two gene regions were found with suggestive linkage (at 11,7 und 40 cM) and on the long arm of chromosome 19 one region was found showing suggestive linkage to birch pollen specific IgG1- titer. For the linkage to chromosome 17 gene regions the MHC-II genes are most likely responsible for. Several other studies found real linkage in these region (De-Sanctis et al., 1995; Zhang et al., 1999; Prows et al., 1997). Furthermore the adapter molecules Vav, Sos and Alk are interesting candidates in these gene region. Human studies found significant linkage in the syngenic regions within the human genome at 6p21-24 in genomewide linkage analysis (Ober et al., 1998; Yokouchi et al., 2000; Anonymous, 1997; Wjst et al., 1999). This study therefore could confirm data of published studies, however further investigation of candidate genes in the suspect regions is required to clarify the basis of birch pollen allergy in mice.