title: Mycobacterium avium subsp. paratuberculosis lipophilic antigen causes Crohn's disease-type necrotizing colitis in Mice.
abstract: BACKGROUND
  A 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced murine colitis model was developed to investigate the pathogenesis and to evaluate a method of treating human Crohn's disease. This experimental model rapidly induces colitis similar to human Crohn's disease lesion in a reproducible manner. However, natural exposure of the human digestive tract to TNBS is unrealistic. A novel animal model based on realistic data is eagerly anticipated in future research on pathogenesis of CD.
  
  
  METHODS
  We evaluated the potency of Map antigen molecules in an effort to develop a novel colitis model using a more realistic source than TNBS. We prepared the Map antigen by ethanol extraction and developed a mouse model in a manner similar to that of the well-known TNBS-induced colitis in mice. In the experiment, seven days after subcutaneous (SC) injection of the antigen into normal C57BL/6 mice, the same antigen in 50% ethanol was injected into the colon by the transanal route with a fine cannula.
  
  
  RESULTS
  On the fifth day after the transanal injection, histopathological examination revealed full-thickness necrotizing colitis with erosion and ulcers; severe infiltration with neutrophils, lymphocytes, macrophages, and perforation. However, no change was detected with each single Map-antigen injection.
  
  
  CONCLUSIONS
  The present results provide a novel animal model for research on CD and may be the key to clarifying the relationship between CD and Map. This is the first evidence that mycobacterium antigen induces necrotizing colitis.
authors.affiliation: Research Area of Pathology and Pathophysiology, National Institute of Animal Health, 3-1-5 Kan-nondai, Tsukuba, 305-0856 Japan.
authors.forename: Eiichi
authors.initials: E
authors.lastname: Momotani
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ozaki
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Hori
authors.forename: Shizuo
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Takashi
authors.initials: T
authors.lastname: Kuribayashi
authors.forename: Shigetoshi
authors.initials: S
authors.lastname: Eda
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ikegami
keywords: Crohn’s disease; IBD; Mice; Mycobacterium; Necrotizing colitis; Paratuberculosis; TNBS