Open AccessDevelopment of colonic adenocarcinomas in a mouse model of ulcerative colitis
Author(s) -
Shah Samir A.,
Simpson Stephen J.,
Brown Lawrence F.,
Comiskey Martina,
de Jong Ype P.,
Allen Deborah,
Terhorst Cox
Publication year - 1998
Publication title -
inflammatory bowel diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.932
H-Index - 146
eISSN - 1536-4844
pISSN - 1078-0998
DOI - 10.1002/ibd.3780040305
Subject(s) - ulcerative colitis , colitis , inflammatory bowel disease , medicine , pathology , staining , histology , gastroenterology , disease
Abstract Mice deficient in both interleukin‐2 and β 2 ‐microglobulin expression (β 2 m null × IL‐2 null 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 β 2 m null × IL‐2 null 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‐γ and TNF‐α. These older β 2 m null × IL‐2 null mice had activated CD4 + T cells as assessed by surface markers on flow cytometry. Cytoplasmic staining revealed IFN‐γ production, but not TNF‐α production by CD4 + T cells. The majority of these older β 2 m null × IL‐2 null mice continued to have colitis on histology. However, they lived much longer and had less wasting in comparison to IL‐2 null mice. At necropsy, 11 (32%) of 34 of the β 2 m null × IL‐2 null 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.