Publication Details

Cd14, Gbp1, and Pla2g2a: three major candidate genes for experimental IBD identified by combining QTL and microarray analyses.

Authors:de Buhr MF, Mhler M, Geffers R, Hansen W, Westendorf AM, Lauber J, Buer J, Schlegelberger B, Hedrich HJ, Bleich A
Title:Cd14, Gbp1, and Pla2g2a: three major candidate genes for experimental IBD identified by combining QTL and microarray analyses.
Journal:Physiological genomics May 2006 , Vol 25 , pp. 426-34
Abstract: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-Tlr4(tm1Aki)) 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.   PUBMED: 16705022
Ontological Annotations:
  • D040641: Quantitative Trait Loci (Publication, NCBO Annotator)
  • MP:0002816: colitis (Publication, NCBO Annotator)
  • GO:0023052: signaling (Publication, NCBO Annotator)
  • D004210: Dissection (Publication, NCBO Annotator)
  • D051379: Mice (Publication, NCBO Annotator)
  • MA:0001524: bowel (Publication, NCBO Annotator)
  • D016753: Interleukin-10 (Publication, NCBO Annotator)
  • D000942: Antigens, Bacterial (Publication, NCBO Annotator)
  • GO:0006955: immune response (Publication, NCBO Annotator)
  • MP:0002169: no abnormal phenotype detected (Publication, NCBO Annotator)
  • D003092: Colitis (Publication, NCBO Annotator)
  • D017737: Macrophages, Peritoneal (Publication, NCBO Annotator)
  • D000941: Antigens (Publication, NCBO Annotator)
  • D010988: Play and Playthings (Publication, NCBO Annotator)
  • D051193: Toll-Like Receptors (Publication, NCBO Annotator)
  • D000818: Animals (Publication, NCBO Annotator)
  • D015153: Blotting, Western (Publication, NCBO Annotator)
  • D009154: Mutation (Publication, NCBO Annotator)
  • D012380: Role (Publication, NCBO Annotator)
  • D008264: Macrophages (Publication, NCBO Annotator)

3 GeneSets from this Publication:

Select gene sets below using the check boxes, and then add them to a project using the pull down below. You can also create a project using the pull down. To view a set, click on the GeneSetID:GeneSet Description shown in green below.
Expand Tier II Mouse 477 Genes GS135562: cytokine deficiency colitis susceptibility 10 (Cdcs10, Published QTL Chr 5)
Expand Tier II Mouse 451 Genes GS135564: cytokine deficiency colitis susceptibility 3 (Cdcs3, Published QTL Chr 2)
Expand Tier II Mouse 694 Genes GS135567: cytokine deficiency colitis susceptibility 9 (Cdcs9, Published QTL Chr 4)