Reference SummaryBerg DJ, J Clin Invest 1996 Aug 15;98(4):1010-20

Title

 Enterocolitis and colon cancer in interleukin-10-deficient mice are associated with aberrant cytokine production and CD4(+) TH1-like responses.

Authors

 Berg DJ; Davidson N; Kuhn R; Muller W; Menon S; Holland G; Thompson-Snipes L; Leach MW; Rennick D

Journal

 J Clin Invest

Volume

 98

Issue

 4

Year

 1996

Pages

 1010-20

Abstract

 We have characterized the progressive stages of chronic intestinal inflammation that develops spontaneously in specific pathogen-free (SPF) mice with a targeted disruption in the IL-10 gene (IL-10-/-). Our longitudinal studies showed that inflammatory changes first appear in the cecum, ascending and transverse colon of 3-wk-old mutants. As the disease progressed, lesions appeared in the remainder of the colon and in the rectum. Some aged IL-10-/- mice also developed inflammation in the small intestine. Prolonged disease with transmural lesions and a high incidence of colorectal adenocarcinomas (60%) was observed in 6-mo-old mutants. Mechanistic studies have associated uncontrolled cytokine production by activated macrophages and CD4+ Th1-like T cells with the enterocolitis exhibited by IL-10-/- mice. A major role for a pathogenic Th1 response was further suggested by showing that anti-IFNgamma antibody (Ab) treatment significantly attenuated intestinal inflammation in young IL-10-/- mice. When weanlings were treated with IL-10, they failed to develop any signs of intestinal inflammation. Interestingly, IL-10 treatment of adults was not curative but did ameliorate disease progression. Our studies have also shown that inheritable factors strongly influence the disease susceptibility of IL-10-/- mice. In 3-mo-old mutants, intestinal lesions were most severe in IL-10-/- 129/SvEv and IL-10-/- BALB/c strains, of intermediate severity in the IL-10-/- 129 x C57BL/6J outbreds, and least severe in the IL-10-/- C57BL/6J strain.

Links

 J:35020 – MGI References
8770874 – National Library of Medicine/PubMed

Strain Notes

Strain Note
B6.129P2-Il10tm1Cgn These mice "were derived by cesarean section under specific-pathogen free conditions at Simonsen Laboratory (Gilroy, CA)."
BALB/c These mice were purchased from the Jackson Laboratory but the substrain was not specified.
Visual Summary Grid

Models
Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
B6;129P2-Il10tm1Cgn Intestine - Large Intestine - Colon - Proximal adenocarcinoma Intestine - Large Intestine - Colon - Proximal

observed
B6;129P2-Il10tm1Cgn Intestine - Large Intestine - Rectum adenocarcinoma Intestine - Large Intestine - Rectum

observed
B6;129P2-Il10tm1Cgn Intestine - Large Intestine adenocarcinoma Intestine - Large Intestine

0 - 67
B6;129P2-Il10tm1Cgn Intestine - Large Intestine adenocarcinoma
  • anti-IFNgamma monoclonal antibody
 Intestine - Large Intestine

0 - 29
B6;129P2-Il10tm1Cgn Intestine - Large Intestine adenocarcinoma
  • interleukin 10 (IL-10)
 Intestine - Large Intestine

0 - 29
B6;129P2 Intestine - Large Intestine adenocarcinoma Intestine - Large Intestine

0
B6.129P2-Il10tm1Cgn Intestine - Large Intestine adenocarcinoma Intestine - Large Intestine

0
C.129P2-Il10tm1Cgn Intestine - Large Intestine adenocarcinoma Intestine - Large Intestine

29
129S6.129P2-Il10tm1Cgn Intestine - Large Intestine adenocarcinoma Intestine - Large Intestine

67
C57BL/6J Intestine - Large Intestine adenocarcinoma Intestine - Large Intestine

0
BALB/c Intestine - Large Intestine adenocarcinoma Intestine - Large Intestine

0
129S6/SvEv Intestine - Large Intestine adenocarcinoma Intestine - Large Intestine

0
B6;129P2-Il10tm1Cgn Intestine - Large Intestine hyperplasia Intestine - Large Intestine

observed