Expanding the utility of the dextran sulfate sodium (DSS) mouse model to induce a clinically relevant loss of intestinal barrier function

PeerJ

article

Kyle E. Cochran¹  Nicholas G. Lamson¹  Kathryn A. Whitehead¹ 

[1] Department of Chemical Engineering, Carnegie Mellon University;Department of Biomedical Engineering, Carnegie Mellon University

关键词: Inflammatory bowel disease;    IBD;    Colitis;    Dextran sodium sulfate;    Dextran sulfate sodium;    DSS;    Animal model;    Intestinal permeability;   

DOI  :  10.7717/peerj.8681

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

BackgroundInflammatory bowel disease (IBD) is a family of debilitating disorders that affects more than 1 million people in the United States. Many animal studies of IBD use a dextran sulfate sodium (DSS) mouse model of colitis that induces rapid and severe colitis symptoms. Although the typical seven-day DSS model is appropriate for many studies, it destroys intestinal barrier function and results in intestinal permeability that is substantially higher than what is typically observed in patients. As such, therapies that enhance or restore barrier integrity are difficult or impossible to evaluate.MethodsWe identify administration conditions that result in more physiologically relevant intestinal damage by systematically varying the duration of DSS administration. We administered 3.0% DSS for four to seven days and assessed disease metrics including weight, fecal consistency, intestinal permeability, spleen weight, and colon length. Histology was performed to assess the structural integrity of the intestinal epithelium.ResultsExtended exposure (seven days) to DSS resulted in substantial, unrecoverable loss of intestinal structure and intestinal permeability increases of greater than 600-fold. Attenuated DSS administration durations (four days) produced less severe symptoms by all metrics. Intestinal permeability increased only 8-fold compared to healthy mice, better recapitulating the 2–18 fold increases in permeability observed in patients. The attenuated model retains the hallmark properties of colitis against which to compare therapeutic candidates. Our results demonstrate that an attenuated DSS colitis model obtains clinically relevant increases in intestinal permeability, enabling the effective evaluation of therapeutic candidates that promote barrier function.

【 授权许可】

CC BY