Comparative severity analysis of colitis in C57BL/6 than BALB/c mice: A novel and rapid model of DSS induced colitis

Abstract

23Colitis is a complex and multifactorial disease with unknown etiology. To understand colitis, a 24 number of models were developed in mouse. Colitis, in these models, was induced using either 25 chemicals or select bacteria. Dextran sulfate sodium (DSS) induced colitis model was used widely, 26 over other models, because of the simpler properties of DSS and similarities of the model with 27 colitis in humans. The available models of DSS induced colitis require either longer time to 28 understand the chronic stages of the disease or a shorter time period to study the acute phase. 29 Currently, no composite models exist that can be used to study the acute, chronic and recovery 30 stages of colitis within a reasonably shorter period of time. In the current study, we have developed 31 a newer model system in two differently immune biased (Th-1 and Th-2) mice strains using DSS. 32 We have developed the DSS model to compare the response in C57BL/6 (Th1 biased) and BALB/c 33 (Th2 biased) mice models. We have standardized the dosage for both C57BL/6 and BALB/c mice 34 with zero mortality rates. Using the model developed we studied the acute, chronic and recovery 35 phases of colitis. The differential responses of C57BL/6 and BALB/c revealed that the disease was 36 more severe in C57Bl/6. BALB/c, on the contrary, recovered from the diseased condition more 37 quickly. The current report will further help to unravel the disease etiology based on 38 immunological background of the host. 39 40 Introduction- 41The mammalian gastrointestinal tract is continuously exposed to numerous microbial pathogenesis 42 well as food-derived and environmental toxins that could lead to diseases such as Crohn's disease 43 (CD) and ulcerative colitis (UC) or inflammatory bowel diseases (IBD) (1). IBD patients show 44 flares of remission and relapses, with symptoms of bloody diarrhoea, abdominal pain, and rectal 45 RAPID COMPARATIVE ASSAY OF COLITIS IN TH1&TH2 BIASED MICE 3 bleeding (1, 2). Although the etiology is unknown, the pathogenesis is likely dependent on the 46 interactions between local immunity and environmental factors in genetically susceptible 47 individuals. Several animal models were developed to understand the pathology of IBD, but no 48 specific model existed for either disease. Gut inflammation can be induced using chemical 49 compounds e.g. DSS or by genetic targeting of specific genes e.g., regulatory cytokines. The 50 majority of the knockout (KO) mice develop colitis with histopathology resembling UC (e.g., IL-2 51 KO mice) or entero-colitis (e.g., IL-10 KO mice) (3). Okayasu and colleagues described a model in 52 which mice, receiving DSS orally, developed acute and chronic colitis resembling UC. The 53 mechanism by which DSS induces intestinal inflammation is unclear but is likely the result of 54 damage to the epithelial monolayer lining of the large intestine (4). The damage to the epithelium 55 may lead to the dissemination of pro-inflammatory intestinal contents (e.g. bacteria and their 56 products) in...

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“…Likewise, DSS induces progressive and severe colitis, enhancing NF-κB activation [289]. C57BL/6 mice with a Th1 genetic background develop severe, chronic DSS-induced colitis, which becomes aggravated over time with ascending doses, whereas BALB/c, with a Th2 genetic background, recover from acute disease upon dose reduction [290]. Overall, the changes in physiological and cytokine profiles observed in the DSS-induced IBD model serve as valuable indicators for investigating IBD's underlying causes and assessing the impacts of potential therapeutic interventions.…”