DESCRIPTION:

QTL associated with cytokine deficiency colitis susceptibility 1. This interval was obtained by using a fixed interval width of 25 Mbp around the peak marker (126744151)

LABEL:

QTL-Cdcs1-Mouse-Chr 3

SCORE TYPE:

Binary

DATE ADDED:

2012-04-02

DATE UPDATED:

2020-05-06

SPECIES:

URI:

http://www.informatics.jax.org/searches/accession_report.cgi?id=MGI:1927809

AUTHORS:

Ermann J, Garrett WS, Kuchroo J, Rourida K, Glickman JN, Bleich A, Glimcher LH

TITLE:

Severity of innate immune-mediated colitis is controlled by the cytokine deficiency-induced colitis susceptibility-1 (Cdcs1) locus.

JOURNAL:

Proceedings of the National Academy of Sciences of the United States of America Apr 2011, Vol 108, pp. 7137-41

ABSTRACT:

Genetic modifier loci influence the phenotypic expression of many Mendelian traits; insight into disease pathogenesis gained from their identification in animal disease models may impact the treatment of human multigenic disorders. We previously described an innate immune-driven model of spontaneous ulcerative colitis in T-bet(-/-).Rag2(-/-) double-deficient mice that resembles human ulcerative colitis. On a BALB/c background, this disease is highly penetrant and results in the development of colorectal cancer. However, we observed that colitis in T-bet(-/-).Rag2(-/-) mice on a C57BL/6 background was significantly less severe. Quantitative trait locus analysis using an N2 backcross strategy revealed a single major quantitative trait locus on chromosome 3 that mapped to the Cdcs1 (cytokine deficiency-induced colitis susceptibility-1) locus previously identified in the Il10(-/-) and Gnai2(-/-) colitis models. Congenic introduction of the susceptible Cdcs1 interval from C3H/He into the C57BL/6 background restored colitis severity. Bone marrow reconstitution experiments further mapped the effect of host genetics on disease severity to the hematopoietic compartment. There were distinct differences in the expression of several Cdcs1 genes in bone marrow-derived dendritic cells from Cdcs1 congenic mice. We conclude that the Cdcs1 locus controls colitis severity in T-bet(-/-).Rag2(-/-) mice through innate immune cells. PUBMED: 21482794
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