B6.129P2-Il10tm1Cgn/J mutant mice spontaneously develop a chronic inflammatory bowel disease (IBD). Il10-deficiency is associated with altered lymphocyte and myeloid profiles, elevated serum amyloid A levels, altered responses to inflammatory or autoimmune stimuli, increased prevalence of colorectal adenocarcinoma, and spontaneous development of chronic enterocolitis. Il10-deficient mice exhibit a significant increase in peripheral blood granulocyte populations upon lesion development.
Dr. Sandy Morse, National Institutes of Health
Mice homozygous for the Il10tm1Cgn targeted mutation are viable and fertile when housed under specific pathogen free (SPF) conditions. Under conventional housing conditions, Il10-deficiency is associated with altered lymphocyte and myeloid profiles, elevated serum amyloid A levels, altered responses to inflammatory or autoimmune stimuli (both endogenous and induced), increased prevalence of colorectal adenocarcinoma (especially on 129/Sv and, to a lesser extent, BALB/c genetic background), and spontaneous development of chronic enterocolitis (see below). As The Jackson Laboratory Repository maintains these mice at high health status conditions (high SPF), the observed or experimentally-induced Il10-deficient phenotype may vary from that previously published using mice from conventional mouse rooms. These IL-10 mutant mice may be useful studying inflammatory bowel disease (IBD) (Crohn's disease (CD) and/or colitis), cancer, innate and adaptive immunity, and many other areas of inflammatory or autoimmunity research.
The onset and severity of both spontaneous and experimentally-induced inflammatory phenotype of Il10-deficient mice is strongly influenced by the genetic background and the husbandry conditions (specific health status/commensal flora) of the vivaria in which mice are maintained.
For example, inflammatory bowel disease (IBD; colitis and Crohn's disease) severity in mouse models is dependent upon interactions between specific genetic background and environmental factors (an as yet undefined component of the enteric flora of which Helicobacter spp. appear to be associated, but not specifically the environmental trigger). Both spontaneous and induced models of IBD demonstrate that susceptibility to intestinal inflammation varies markedly among inbred strains of mice. Generally, for Il10-deficient models on defined genetic backgrounds, the severity of colitis-related characteristics is most severe on C3H/HeJBir (Stock No. 004326 and Stock No. 003968) or 129/Sv (Stock No. 004368), intermediate on BALB/cJ (Stock No. 004333) or NOD/Lt (Stock No. 004266), and least severe on C57BL/10 (Stock No. 002250) or C57BL/6J (Stock No. 002251). Furthermore, the husbandry conditions (specific health status/commensal flora) of the vivaria in which mice are maintained significantly alter the onset and severity of spontaneous IBD; higher SPF conditions are associated with attenuated colitis. Il10-deficient mice on both the C3H/HeJBir and C57BL/6J genetic backgrounds exhibit a significant increase in peripheral blood granulocyte populations upon lesion development and this metric may be used as a robust non-lethal assessment of Il10-deficiency induced colitis onset and severity. Other indications of Il10-deficiency induced colitic lesion onset may include perianal ulceration (C3H/HeJBir background) or rectal prolapse (C57BL/6J background).
The Il10tm1Cgn mutation was created by in the Laboratory of Dr. Werner Muller at the University of Cologne. Briefly, a targeting vector was designed to replace codons 5-55 of exon 1 of the targeted gene with a 24 bp linker (providing a termination codon) and a neo expression cassette, as well as introduce a termination codon into exon 3. The construct was electroporated into 129P2/OlaHsd-derived E14-1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient C57BL/6 blastocysts and chimeric males were bred with C57BL/6 females to establish the mutant colony on a mixed B6;129P2 genetic background. Subsequently, mutant mice were backcrossed to the C57BL/6J genetic background for several generations to generate this strain.
|Allele Name||targeted mutation 1, University of Cologne|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||IL-10 KO; IL-10-; IL-10KO; IL-10KO; Il10-; Il10tmCgn|
|Gene Symbol and Name||Il10, interleukin 10|
|Gene Synonym(s)||CSIF; GVHDS; IL-10; IL10A; IL10X; Il-10; TGIF; cytokine synthesis inhibitory factor|
|Strain of Origin||129P2/OlaHsd|
|Molecular Note||A 500 bp genomic fragment containing codons 5-55 was replaced with a linker containing a termination codon followed by a neomycin cassette. A termination codon was also introduced into exon 3. No IL10 activity was detectable by ELISA assays in supernatants of in vitro cultures of Con A-stimulated splenic T cells derived from homozygous mice following infection with the nematode N. brasiliensis.|
|Mutations Made By|| |
Dr. Ralf Kuhn, University of Cologne
When maintaining a live colony, homozygous mice may be bred together. As homozygous mice are more susceptible to pathogenic bacteria, high specific pathogen-free (SPF) conditions are recommended for optimal breeding. However, the onset and severity of both the spontaneous and experimentally-induced inflammatory phenotype of Il10-deficient mice is strongly influenced by the genetic background and the husbandry conditions (specific health status/commensal flora) of the vivaria in which mice are maintained and such high SPF conditions may attenuate the desired Il10-deficient phenotype.
|Please inquire about possible genotypes.|
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided,
their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of
each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders
are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in
order to provide the minimum number of animals, animals will ship within 25 weeks.
The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.
Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation.
"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCT(S)" means biological materials supplied by JACKSON, and their derivatives. "SERVICES" means projects conducted by JACKSON for other parties that may include but are not limited to the use of MICE or PRODUCTS. "RECIPIENT" means each recipient of MICE, PRODUCTS, or SERVICES provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE, PRODUCTS or SERVICES from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON’s prior written authorization.
MICE, PRODUCTS AND SERVICES ARE PROVIDED "AS IS". JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.
In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of, PRODUCTS or SERVICES, JACKSON will, at its option, provide credit or replacement for the PRODUCT received or the SERVICES provided; JACKSON makes no other representations and this shall be the exclusive remedy of the purchaser. Please note specific policy for live mice.
Consistent with the requirement for a written understanding regarding animal care and use, the JACKSON Animal Care and Use Committee will review the animal care and use protocol(s) associated with any SERVICES to be performed at JACKSON, and JACKSON shall have ultimate responsibility and authority for the care of animals while on site or in JACKSON custody.
In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS, or SERVICES, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS, or SERVICES from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.
MICE, PRODUCTS or SERVICES are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.
The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or SERVICES. In addition, special terms and conditions of sale of certain MICE, PRODUCTS, or SERVICES may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and SERVICES by JACKSON, and by its licensees and distributors.
Acceptance of delivery of MICE, PRODUCTS or SERVICES shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or SERVICES by JACKSON.