Publication Details

A major quantitative trait locus on chromosome 3 controls colitis severity in IL-10-deficient mice.

Authors:Farmer MA, Sundberg JP, Bristol IJ, Churchill GA, Li R, Elson CO, Leiter EH
Title:A major quantitative trait locus on chromosome 3 controls colitis severity in IL-10-deficient mice.
Journal:Proceedings of the National Academy of Sciences of the United States of America Nov 2001 , Vol 98 , pp. 13820-5
Abstract:Colitic lesions are much more severe in C3H/HeJBir (C3H) than C57BL/6J (B6) mice after 10 backcrosses of a disrupted interleukin-10 (Il10) gene. This study identified cytokine deficiency-induced colitis susceptibility (Cdcs) modifiers by using quantitative trait locus (QTL) analysis. A segregating F(2) population (n = 408) of IL-10-deficient mice was genotyped and necropsied at 6 weeks of age. A major C3H-derived colitogenic QTL (Cdcs1) on chromosome (Chr.) 3 contributed to lesions in both cecum [logarithm of odds ratio (LOD) = 14.6)] and colon (LOD = 26.5) as well as colitis-related phenotypes such as spleen/body weight ratio, mesenteric lymph node/body weight ratio, and secretory IgA levels. Evidence for other C3H QTL on Chr. 1 (Cdcs2) and Chr. 2 (Cdcs3) was obtained. Cdcs1 interacted epistatically or contributed additively with loci on other chromosomes. The resistant B6 background also contributed colitogenic QTL: Cdcs4 (Chr. 8), Cdcs5 (Chr. 17, MHC), and Cdcs6 (Chr. 18). Epistatic interactions between B6 QTL on Chr. 8 and 18 contributing to cecum hyperplasia were particularly striking. In conclusion, a colitogenic susceptibility QTL on Chr. 3 has been shown to exacerbate colitis in combination with modifiers contributed from both parental genomes. The complex nature of interactions among loci in this mouse model system, coupled with separate deleterious contributions from both parental strains, illustrates why detection of human inflammatory bowel disease linkages has proven to be so difficult. A human ortholog of the Chr. 3 QTL, if one exists, would map to Chr. 4q or 1p.   PUBMED: 11707574
Ontological Annotations:
  • MA:0002520: lymph (Publication, NCBO Annotator)
  • D040641: Quantitative Trait Loci (Publication, NCBO Annotator)
  • MP:0002816: colitis (Publication, NCBO Annotator)
  • D006801: Humans (Publication, NCBO Annotator)
  • D007071: Immunoglobulin A, Secretory (Publication, NCBO Annotator)
  • D002875: Chromosomes (Publication, NCBO Annotator)
  • D001835: Body Weight (Publication, NCBO Annotator)
  • MA:0000139: lymph node (Publication, NCBO Annotator)
  • D051379: Mice (Publication, NCBO Annotator)
  • MA:0000334: cecum (Publication, NCBO Annotator)
  • MA:0001524: bowel (Publication, NCBO Annotator)
  • D016753: Interleukin-10 (Publication, NCBO Annotator)
  • D002893: Chromosomes, Human, Pair 3 (Publication, NCBO Annotator)
  • GO:0005694: chromosome (Publication, NCBO Annotator)
  • D003092: Colitis (Publication, NCBO Annotator)
  • MA:0000141: spleen (Publication, NCBO Annotator)
  • D007070: Immunoglobulin A (Publication, NCBO Annotator)
  • D008198: Lymph Nodes (Publication, NCBO Annotator)
  • D002432: Cecum (Publication, NCBO Annotator)
  • D016017: Odds Ratio (Publication, NCBO Annotator)
  • D019368: Nature (Publication, NCBO Annotator)
  • D013154: Spleen (Publication, NCBO Annotator)
  • D003106: Colon (Publication, NCBO Annotator)
  • MA:0002829: mesenteric lymph node (Publication, NCBO Annotator)
  • MA:0000335: colon (Publication, NCBO Annotator)
  • D006965: Hyperplasia (Publication, NCBO Annotator)
  • D008196: Lymph (Publication, NCBO Annotator)
  • D015212: Inflammatory Bowel Diseases (Publication, NCBO Annotator)

1 GeneSets from this Publication:

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Expand Tier II Mouse 353 Genes GS135563: cytokine deficiency colitis susceptibility 2 (Cdcs2, Published QTL Chr 1)