Table 1. Selected spontaneous and transgenic rodent IBD models.

Mouse Nomenclature	Genetic Modification	Resultant Pathophysiologic Outcome	Clinical Disease	Pathologic Disease Expression	LAR Health Status require for IBD expression
ITF-dnRII1	Overexpression of the dominant-negative TGFβ type II receptor	Functional inactivation of TGFβRII protein expression	Weight loss, diarrhea, hematochezia, anal / rectal prolapse	Severe ulcerative mucosal ulceration; severe inflammation	Specific Pathogen Free + Dextran Sodium Sulfate
Smad-32	Deficient in TGFβ signaling molecule smad3	Disruption of exon 2, smad3 TGFβRII sequence	Diminished size, diarrhea, gastric and deeply invasive colorectal tumors	Colonic epithelial crypt herniation, chronic - active repair, colonic neoplasia	Specific pathogen free
dnKO3	Dominant negative TGFβRII mice crossed with class II cytokine receptor family member 2	Deficient in TGFβRII and cytokine receptor family member; null mutants for IL10RII	Failure to thrive, rapid weight loss and early mortality	Severe UC with Focal ulceration, mucosal thickening in the cecum, descending colon and rectum; mild ascending colonic change with minimal inflammation; severe mucosal inflammation with mixed infiltrates
TNFΔARE 4	Deletion ARE 3'UTR regulatory element for tumor necrosis factor	Loss of posttranscriptional regulation for TNF type I or II receptors	Severe weight loss, early disease onset by D10 postnatal and mortality by 5 weeks; inflammatory polyarthritis and CD bowel disease	Ileitis with minimal colonic involvement; consistent with Th-1 cytokine activation pattern expression
T/I mice- (B6.129S6-Tnftm1Gkl/J) (Tnf+/-Il10-/- [T-het/I] and Tnf-/-Il10-/-/J)5	IL-10-/- KO crossed with knockout TNF-deficient KO	Deficient in IL10 and TNF resulting in mucosal compromise and increased inflammation	Spontaneous colonic tumors immediately after weaning	UC-linear continuous inflammation of the terminal colon and rectum after 15 weeks of age. Neutrophilic lamina propria infiltrates, crypt abscesses and mucosal ulceration; colonic cancer various phenotypes	Specific pathogen free; phenotype prevented by exogenous treatment with drug cocktail consisting of amoxicillin, clarithromycin, metronidazole antibiotics and omeprazole acid suppression agent
SAMP1, SAMP1/Yit/Fc TG mice6	STAT3 activation and inflammation	Early activation of Th1 mediated pathways; mucosa immunity dysbiosis; recent suggestion of Th2 activation also	Diarrhea	UC-spontaneous ileitis with skip lesions, mixed chronic active inflammation infiltrates. G granulomatous inflammation at 10 weeks of age, 100 % penetrance by 30 weeks; severe bowel strictures mature adults in older than 40 weeks of age CD-spontaneous gastritis and autoimmune hepatitis	Specific pathogen free
Wiskott-Aldrich Syndrome protein (WASP) deficient Tg mice7	Deletion of WASP sequence	Absence of WASP expression in hematopoietic cells with lack of integration between surface receptor and actin cytoskeleton signaling networks	Weight loss, diarrhea, rectal prolapse; include lymphopenia, thrombocytopenia, cytoskeletal abnormalities; T cell signaling defects and l quantity; early mortality by 3 months; 100 % penetrance by 6 months in surviving mice	Mixed cell infiltrates in colonic lamina propria; crypt abscesses, absence of granulomas; increased cytokine expression and abnormal Treg number and activity
HLA-B27 Tg rat8	Multiple inserted integrated, HLA-B27 gene; multiple Tg rat strain constructs	HLA protein misfolding promotes inflammation	Diarrhea by 10 weeks of age followed by peripheral arthritis; spondyloarthropathies with multifocal severe arthritis; severe inflammation of the bowel, bone, joints and skin	CD: Marked inflammation in epithelium of the stomach, large and small intestine	Requires conventional health status management for disease expression
				UC-mucosal ulceration; Th1 cytokine expression
NOD2 Tg mice9	Deletion of exons 1, 3, and a frameshift deletion	Deficiency of intracellular receptor for bacterial wall component muramyl dipeptide; altered TLR2 expression; deficient NOD expression; loss of mucosal barrier function	Increased susceptibility to infection		Model severity is increased with specific pathogen free or gnotobiotic health status; associated with administration of dextran sodium sulfate;
NF-κB essential modulator (NEMO) Tg mice10		Loss of regulation for intestinal homeostatic growth, inflammation and tight junctional permeability	In some Nemo/mice strains early mortality; related strains Ikk2/mice die in utero at embryonic day 12.5	Massive apoptosis in the liver; in Ikk1/mice, skeletal defects, thickening of the skin and impaired limb outgrowth, but normal liver development
stat5IECKO KO mice11	Deficiency of STAT5 and increased NF-κB activation	Deficient maintenance of zonula occulens protein: cytoskeletal junctional stability; loss of colonic barrier function	Rectal bleeding, shortened colon, slow weight gain, stool quality that was soft to frank diarrhea	Severe ileitis and colitis due to persistent barrier dysfunction and impairment of mucosal wound healing Requires dextran sodium sulfate for model expression
IKK-NEMO/IKKαβ10,12	Double knockout with conditional targeting of the NRMO regulatory complex governing NFκB signaling	Defective TGFβRII and IL10RII; overactive T cell populations	Diarrhea and weight loss	UC and CD: Severe chronic fulminant ulcerative pancolitis	Completely reversible with broad spectrum antibiotics
K8-/- keratin TG mice 13	Several Tg constructs available;	Defective intermediate filament class keratin 8, 18 and 19 expression; Defective TNFRII-mediated and TNF-induced transcription factor signaling and activation; mistargeted protein translocation; abnormal intestinal microbiota growth rates and species distribution	Diarrhea; abnormal Cl- transport	Colonic inflammation; epithelial marker expression relocated from basal crypts to apical and lateral locations
				Human IBD associated with abnormal intermediate filament expression for keratins 8, 18 and 19
XBP-1 Tg mice14	Defective UPR and partial Xbp1 deficiency in the colon	Develop abnormal unfolded protein during intestinal inflammation		Suppressed colitis development; paneth and goblet cell apoptosis, spontaneous ileal inflammation; MGUS and multiple myeloma Increased sensitivity to dextran sodium sulfate colitis induction
Ire1β-/- KO mice15	No cleavage of Xbpr mRNA	Loss of the Ire1β UPR endonuclease		No spontaneous intestinal inflammation
				Increased sensitivity to dextran sodium sulfate colitis induction
Agr2-/- mice16	Conditional allele or inducible knockout mice for expression of a the protein disulfide isomerase (PDI)	Loss of intermolecular disulfide bond formation reduction for correction of misfolded proteins prior to removal; Deficient Muc2 biosynthesis	Rectal prolapse; diarrhea, weight loss and hematochezia with colitis induction	Lack of mucus production in the intestine; paneth and goblet cell apoptosis Endoplasmic reticular stress; Inducible and germline KO mice: spontaneous severe terminal ileitis and colitis with neutrophillic and granulomatous responses
BIN Tg mice17	Ablate BIN1 sequence		Protective effect-no clinical signs with use of physiological stressors	No histopathological changes noted Increased functional resistance to dextran sodium sulfate-induced colitis
IL23p19 KO and Il12p35 KO mice18	Ablate cytokine sequence	Variation in T cell populations and cytokine release patterns	Modified immunoreaction to enteric commensal bacterial populations and mucosal epithelial defense
STAT3 deficiency Tg mice19	Ablate STAT3 sequence	STAT3 deficiency; nonspecific transcription factor that opposes cytokine expression and induces IL23R expression and Th17 differentiation.	Severe dehydration, lethargy, weight loss, diarrhea, anal bleeding and prolapse by day 11; Severe mixed inflammatory infiltrate in multiple sites; colon enlargement, hematochezia and diarrhea	Responsive to polyI:polyC Immunostimulant treatment: clinical wasting syndrome with severe fatal enterocolitis within 2 to 3 weeks after treatment
				-Inflammatory Response is obliterated by neutralizing anti-p40 antibodies
IL10-/- and TCRα-/- Tg mice20	Multiple constructs. Deficient in IL10 and TCRá sequence; alternative strain construction available for IL10 and TCRβ	Variable phenotype depending on construct; IL10-/- when expressed on 129/SvEv, BALB/c, and C3H/HeJBir backgrounds exhibit increased IBD phenotypical susceptibility	UC-TCRα-/- mice exhibit mucosal inflammation andTh2 associated immunoreactivity at 12 weeks of age	Spontaneous intestinal inflammation with STAT3 present in circulating macrophages	Limited IL10-/- and/or TCRα-/- model disease expression when maintained under germ free or defined enteric commensal conditions
			CD: IL10-/- mice exhibit chronic enterocolitis and Th1 associated immunoreactivity
Non Obese Diabetic (NOD) based IL10 deficient Tg21 mice	Many constructs available.		Rectal prolapse; Absence of diabetes mellitus and decreased sialodacryadenitis		Conventional facility health status management

References to each model are as follows: ¹[51,52,53]. ²http://jaxmice.jax.org/strain/003451.html; ³[54]; ⁴[56]; ⁵http:/jaxmice.jax.org/strain/003008.html; ⁶[61,62,87]; ⁷[50,65]; ⁸[68]; ⁹[33]; ¹⁰[26,45,88]; ¹¹[26]; ¹²[54]; ¹³[71]; ¹⁴[33,68]; ¹⁵[68], http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE6980; ¹⁶[68,72], http://jaxmice.jax.org/strain/025630.html;¹⁷[77]; ¹⁸[33]; ¹⁹[7,45,78]; ²⁰[8,45,59], http://jaxmice.jax.org/list/ra1655.html, http://jaxmice.jax.org/jaxnotes/502/502a.html; ²¹[8,59]