- Useful for studying colitis and immunoregulatory pathways
- Carries a deletion of the entire Il10 coding sequence
- Homozygous mice do not produce the anti-inflammatory cytokine IL-10
- Colitis severity and onset are expected to vary by genetic background in Il10 knockouts, with reported earlier onset and greater severity in BALB/c vs. C57BL/6 backgrounds (J Clin Invest. 1996 Aug 15;98(4):1010-20)
- Colitis in this model is highly microbiome-dependent; disease severity and age of onset will be affected by different facility microbiomes (Infect Immun. 1998 Nov;66(11):5224-31)
- Although germ-free Il10 knockouts do not develop colitis (Infect Immun. 1998 Nov;66(11):5224-31), the introduction of select microbes or fecal microbiomes induces rapid colitis onset in adult animals (Inflamm Bowel Dis. 2007 Dec;13(12):1457-66).
- Available at the Germ Free and Excluded Flora health standards to enable microbiome research
- Order model #15660 for Excluded Flora or model #GF-15660 for Germ Free
- Phenotype update: Feedback from a pharma customer who received female 15660 mice from Taconic is that spontaneous colitis occurred in all vehicle treated animals. The disease progressed slowly without remission, with clinical onset at 15 wk of age until study termination at 20 wk of age. A clinically-relevant drug treatment was effective in reducing disease progression.
Guidance for selecting the most appropriate Il10 Knockout model for your research:Orders by weight:
- The BALB/c Il10 Knockout at the Excluded Flora health standard (Taconic model #15660) is appropriate for studies involving rapid spontaneous disease onset. This model may be best for routine screening of new colitis therapeutics.
- The C57BL/6 Il10 Knockout is no longer available at the Excluded Flora health standard, but Germ Free mice can be associated with your flora of choice. It can also be used for crossbreeding to other GEMs on the C57BL/6 background, for example to study whether crossing to a particular knockout results in more or less severe disease as an insight into IBD mechanisms. Inquire for details on a crossbreeding license.
- The Germ Free Il10 Knockouts (Taconic model #GF-15660 for BALB/c background or GF-16006 for C57BL/6 background) are the most appropriate models for microbiome studies, including investigations of mono-associations, specific complex microbiota compositions or patient-derived microbiota samples. Association of Germ Free Il10 Knockout mice can provide cohorts which develop accelerated and synchronized disease, which may cut down the timeline for drug screening.
Taconic cannot accept orders by weight for this model. Please note that shipments may contain animals with a larger weight variation.Availability:
EF animals available now. GF animals expected to be available in late 2018/early 2019.
Genetic Background: BALB/cAnNTac Background
Origin: The Il10 knockout mouse was developed by Taconic Biosciences. The model was created through CRISPR/Cas9-mediated gene editing to delete the entire Il10 locus (exons 1 to 5, including the proximal promoter and UTRs). Targeting occurred in BALB/cAnNTac embryos. The selected G1 founder was screened for off-target effects and the targeted locus was sequenced to confirm targeting specificity. Heterozygous animals were intercrossed to generate homozygous mice. The line is maintained by incrossing homozygous mice.
There is no specific publication describing the generation of these mice. The initial publication describing application of these mice is as follows:
Covington, M., et al. Preclinical Characterization of Itacitinib (INCB039110), a Novel Selective Inhibitor of JAK1, for the Treatment of Inflammatory Diseases. European Journal of Pharmacology 2020, 885:173505
Additionally, multiple publications exist demonstrating applications using similar models. See reference list.Other Publications:
Kühn R, Löhler J, Rennick D, Rajewsky K, Müller W. Interleukin-10-deficient mice develop chronic enterocolitis. Cell. 1993 Oct 22;75(2):263-74
Berg DJ, Davidson N, Kühn R, Müller W, Menon S, Holland G, Thompson-Snipes L, Leach MW, Rennick D. Enterocolitis and colon cancer in interleukin-10-deficient mice are associated with aberrant cytokine production and CD4(+) TH1-like responses. J Clin Invest. 1996 Aug 15;98(4):1010-20
Sellon RK, Tonkonogy S, Schultz M, Dieleman LA, Grenther W, Balish E, Rennick DM, Sartor RB. Resident enteric bacteria are necessary for development of spontaneous colitis and immune system activation in interleukin-10-deficient mice. Infect Immun. 1998 Nov;66(11):5224-31
Kim SC, Tonkonogy SL, Karrasch T, Jobin C, Sartor RB. Dual-association of gnotobiotic IL-10-/- mice with 2 nonpathogenic commensal bacteria induces aggressive pancolitis. Inflamm Bowel Dis. 2007 Dec;13(12):1457-66