IL10 deficiency

Abstract: Interleukin-10-deficient (Il10-/-) mice serve as a model for inflammatory bowel disease (IBD). The severity of colitis strongly depends on the inbred strain carrying the disrupted Il10 gene: C3H/HeJBir (C3) confers disease susceptibility, whereas C57BL/6J (B6) confers resistance. Genome-wide scans with microsatellite markers on segregrating backcross and F2 populations resulted in the detection of ten colitogenic quantitative trait loci (QTL). The aim of this study was to reduce the large number of candidate genes within the QTL intervals by identifying those genes which are located within the candidate gene intervals and which are differentially expressed in the colon of IBD-susceptible and -resistant strains. Using this combination of QTL mapping and microarray analysis, we identified 16 genes which were differentially expressed between B6- and C3-Il10-/- mice and were located within the candidate gene intervals. Three of these genes (Pla2g2a, Gbp1, Cd14) showed prominent differences in expression levels between B6- and C3-Il10-/- as well as between B6 and C3 wildtype mice and were considered to be major candidate genes. Pla2g2a and Gbp1 are known to be polymorphic between C3 and B6 mice. Expression data for Cd14 were confirmed by real-time RT PCR using specified pathogen free and germfree Il10-/- mice. In conclusion, the large number of candidate genes was reduced to three major candidates by using a combination of QTL mapping and microarray analysis. All three genes play an important role in inflammatory processes and immune response.

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de Buhr MF, Mähler M, Geffers R, Hansen W, Westendorf AM, Lauber J, Buer J, Schlegelberger B, Hedrich HJ, Bleich A