The SCID/SCID.bg/bg Mouse Infected With My Cobacterium Paratuberculosis For The Study Of Paratuberculosis

Abstract

.The goal of this study was to evaluate the severe combined immunodeficient! beige (SCID bg) mouse infected with Mycobacterium paratuberculosis as a laboratory animal model for the study of paratuberculosis. Mice injected intraperitoneally with M. paratuberculosis lost body weight and consistently developed histologic lesions with acid-fast bacilli in the liver, spleen and intestine. The reason for body weight loss. was determined in a pair feeding experiment from which it was concluded that .weight loss was due in part to reduced food intake. Both infected and uninfected mice (the latter on restricted food intake) had lost carcass dry matter. However, infected mice appeared to have maintained their body weights as a result of retaining body water (presumably edema). Villi of the distal small intestine of infected SCID bg mice increased in width, and the submucosa. and lamina propria were infiltrated with inflammatory cells. In vitro Using chamber studies showed high baseline potential difference and decreased conductance across the distal small intestine. The change in short circuit current, following transmural electrical stimulation or exposure to glucose, was significantly reduced, suggesting neural and/or intestinal epithelial cell damage. Thus minor morphologic changes, but significant alteration in intestinal transport function were observed. SCID bg mice inoculated with M. paratuberculosis and later reconstituted with 3.0 X 107 spleen cells from either naive or BALB/c mice previously infected with M. paratuberculosis had reduced severity of clinical disease , macroscopic and microscopic lesions, and bacterial load compared to infected but nonreconstituted mice. However, in vitro Ussing chambers studies of distal small intestine of infected but not reconstituted mice showed a poor response to transmural stimulation, and to the addition of glucose, histamine and forskolin and the responses of mice reconstituted with naive cells appeared to be further reduced. Thus immune reconstitution of SCID bg mice reduced the severity of clinical disease and pathologic lesions, but appeared to enhance intestinal inflammation and intestinal path physiology. This research has confirmed the hypothesis that the SCID bg mouse is a valuable laboratory animal model for studies on the pathogenesis and immunology of paratuberculosis.