Document Detail


A major quantitative trait locus on chromosome 3 controls colitis severity in IL-10-deficient mice.
MedLine Citation:
PMID:  11707574     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
M A Farmer; J P Sundberg; I J Bristol; G A Churchill; R Li; C O Elson; E H Leiter
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.     Date:  2001-11-13
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  98     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2001 Nov 
Date Detail:
Created Date:  2001-11-21     Completed Date:  2002-01-08     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  13820-5     Citation Subset:  IM    
Affiliation:
The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Chromosomes
Colitis / genetics*,  pathology,  physiopathology
Epistasis, Genetic
Female
Interleukin-10 / genetics,  immunology*
Linkage (Genetics)
Male
Mice
Mice, Inbred C3H
Mice, Inbred C57BL
Mice, Knockout
Quantitative Trait, Heritable*
Grant Support
ID/Acronym/Agency:
CA-34196/CA/NCI NIH HHS; PPG-44240/PG/OAPP OPHS HHS
Chemical
Reg. No./Substance:
130068-27-8/Interleukin-10
Comments/Corrections

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