Development of colonic adenocarcinomas in a mouse model of ulcerative colitis.
Mice deficient in both interleukin-2 and beta 2-microglobulin expression (Beta 2mullnull x IL-2null mice) develop an inflammatory disease of the colon resembling ulcerative colitis. To examine long-term complications of disease in these mice, a group of 34 Beta 2mnull x IL-2null mice was monitored for 6-12 months. Development of clinical disease was assessed by wasting, general appearance, and diarrhea. Further analysis included histologic examination of the distal colon for colitis, staining of CD4+ T cells for surface activation markers, and cytoplasmic staining of CD4+ T cells for IFN-gamma and TNF-alpha. These older Beta 2mnull x IL-2null mice had activated CD4+ T cells as assessed by surface markers on flow cytometry. Cytoplasmic staining revealed IFN-gamma production, but not TNF-alpha production by CD4+ T cells. The majority of these older Beta 2mnull x IL-2null mice continued to have colitis on histology. However, they lived much longer and had less wasting in comparison to IL-2null mice. At necropsy, 11 (32%) of 34 of the Beta 2mnull x IL-2null mice had tumors in the proximal half of the colon. Histologic examination confirmed these tumors to be adenocarcinomas. These mice may be useful as a model for studying carcinogenesis in chronic colitis.
Shah
S A
SA
Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
Simpson
S J
SJ
Brown
L F
LF
Comiskey
M
M
de Jong
Y P
YP
Allen
D
D
Terhorst
C
C
D000230:Adenocarcinoma / Q000209:etiology* / Q000473:pathology; D000818:Animals; D003093:Colitis, Ulcerative / Q000150:complications* / Q000276:immunology; D003110:Colonic Neoplasms / Q000209:etiology* / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D007376:Interleukin-2 / Q000172:deficiency* / Q000235:genetics; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D015203:Reproducibility of Results; D013601:T-Lymphocytes / Q000276:immunology; D001613:beta 2-Microglobulin / Q000172:deficiency* / Q000235:genetics
D007376:Interleukin-2; D001613:beta 2-Microglobulin