Cd14,Gbp1, andPla2g2a: three major candidate genes for experimental IBD identified by combining QTL and microarray analyses
Copyright policy )Cd14,Gbp1, andPla2g2a: three major candidate genes for experimental IBD identified by combining QTL and microarray analyses
Induction of inflammatory bowel (IBD)-like disease in mice by a targeted mutation in the Il10 gene ( Il10−/−) is inbred strain dependent. C3H/HeJBir (C3) mice are colitis susceptible, whereas C57BL/6J (B6) mice are resistant. Genetic dissection of this susceptibility revealed 10 colitogenic quantitative trait loci (QTL). The aim of this study was to identify valuable candidate genes by a combination of QTL mapping and microarray analyses. Sixteen genes were differentially expressed between B6- and C3- Il10−/−mice and were located within the QTL intervals. Three major candidate genes ( Cd14, Gbp1, Pla2g2a) showed prominent expression differences between B6- and C3- Il10−/−as well as between B6 and C3 wild-type mice, which was confirmed by semiquantitative or real-time RT-PCR. Because strain differences are known for Gbp1 and Pla2g2a, further analyses focused on Cd14. Western blot analysis revealed strain differences also on the protein level. Cd14 expression in animals with defective and intact Toll-like receptor (TLR)4 signaling (C3, C3H/HeN, B6, B6- Tlr4tm1Aki) make the TLR4 defect of C3 mice unlikely to be the reason for higher Cd14 expression. Less Cd14 expression in germ-free mice indicates a contribution of the microflora on Cd14 expression. Stimulation of naive peritoneal macrophages with bacterial antigens showed lower CD14 surface expression in B6 than in C3 mice. In conclusion, the large number of candidate genes was reduced to three major candidates that play an important role in inflammatory processes and immune response. Strain differences for them are already known or are shown in this study.
- Helmholtz Association of German Research Centres Germany
- Institute of Medical Microbiology and Hygiene Germany
- Helmholtz Center for Information Security Germany
- Institute of Laboratory Animal Science China (People's Republic of)
- Hannover Medical School Germany
Mice, Knockout, Antigens, Bacterial, Mice, Inbred C3H, Colon, Gene Expression Profiling, Quantitative Trait Loci, Medizin, Lipopolysaccharide Receptors, Inflammatory Bowel Diseases, Group II Phospholipases A2, Phospholipases A, Interleukin-10, Mice, Inbred C57BL, Mice, GTP-Binding Proteins, Macrophages, Peritoneal, Animals, Colitis, Ulcerative, RNA, Messenger, Cells, Cultured, Oligonucleotide Array Sequence Analysis
Mice, Knockout, Antigens, Bacterial, Mice, Inbred C3H, Colon, Gene Expression Profiling, Quantitative Trait Loci, Medizin, Lipopolysaccharide Receptors, Inflammatory Bowel Diseases, Group II Phospholipases A2, Phospholipases A, Interleukin-10, Mice, Inbred C57BL, Mice, GTP-Binding Proteins, Macrophages, Peritoneal, Animals, Colitis, Ulcerative, RNA, Messenger, Cells, Cultured, Oligonucleotide Array Sequence Analysis
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