Table 2.

Commonly used IBD mouse models.

Categories	Model examples	Prevalent type of response	Details of barrier defect	References
Chemical induction	Dextran sodium sulfate (DSS) colitis	Epithelial damage	Deficiency of Muc2, main gastrointestinal mucin.	Persše and Cerar, 2012; Chassaing et al., 2014
	2,4,6-trinitrobenzene sulfonic acid (TNBS)	Epithelial damage, immune-mediated	Coupled with intestinal proteins eliciting significant immunologic response, such as Th1 inflammatory response.	Loeuillard et al., 2014
	Oxazolone	Epithelial damage, immune-mediated	Direct destruction of colonic mucosa and association with Th2-type inflammatory response.	Heller et al., 2002; Weigmann and Neurath, 2016
Spontaneous mutation	SAMP1/Yit	Immune-mediated	Spontaneous inflammation of terminal ileum and cecum driven by TH1 response and epithelial barrier defect, but TH2 response may develop at later stages of disease.	Pizarro et al., 2011
	C3H/HeJBir	Immune-mediated	Increased B-cell and T-cell reactivity to antigens of enteric bacterial flora causing colitis.	Elson et al., 2000
	Nuclear factor κB (NF-κB) essential modulator (NEMO) colitis	Cytokine release	Reduced paneth cell numbers and increased IEC apoptosis.	Liu et al., 2017
Adoptive T-cell transfer	Systemic T-cell activation	Immune-mediated	Cytokine release (TNF, LIGHT) causing MLCK activation and occludin endocytosis.	Chen and Sundrud, 2016
	CD4 + CD45RBhi	Immune-mediated	CD4+ cells from diseased mice displayed highly polarized Th1 pattern of cytokine synthesis.	Byrne et al., 2005
Genetic engineering	IL-10−/− knockout	Cytokine release, epithelial damage	IL-10 signaling in macrophages and neutrophils is necessary to prevent abnormal regulation of responses to normal microflora.	Scheinin et al., 2003
	FOXP3 mutation	Immune-mediated	Autoimmune enteropathy by excessive T-cell activation.	Bamidele et al., 2018
	Dominant negative N-cadherin transgene expression	Epithelial damage	Defective epithelial maturation, migration, and adherens junctions.	Radice, 2013
	MDR1A-deficient mice	Epithelial damage	Reduced occludin phosphorylation, increased epithelial cell response to LPS.	Wilk et al., 2005
	Constitutively active MLCK transgene expression	Epithelial damage	MLC hyperphosphorylation, barrier dysregulation.	Cunningham and Turner, 2012
	JAM-A-deficient mice	Epithelial damage	Effect on epithelial permeability.	Laukoetter et al., 2007
	Mucin-2-deficient mice	Epithelial damage	Intercellular junction defects, mitochondrial damage, and ATP depletion.	Borisova et al., 2020
Microbiome induction	Enteropathogenic Escherichia coli infection	Immune-mediated	Type III secretion (of bacterial proteins), MLCK activation, and occludin endocytosis.	Glotfelty and Hecht, 2012
	Clostridium difficile-induced colitis	Epithelial damage	Actomyosin disruption and glucosylation of Rho proteins, loss of ZO1 and ZO2.	Best et al., 2012
	Enteric microbial transfer to germ-free IL-10−/− mice	Immune-mediated	Resident enteric bacteria are necessary for the development of spontaneous colitis and immune system activation in IL-10-deficient mice.	Keubler et al., 2015