CBA.129P2(B6)-Il10^tm1Cgn/TrnrJ

Stock number: 036145
Product name: CBA/J IL-10-/-
Research areas: Cancer Research, Hematological Research, Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

This CBA/J Il10-deficient mouse model is relatively susceptible to Mycobacterium tuberculosis infection and is capable of forming mature, fibrotic M. tuberculosis-containing protective pulmonary granulomas similar to those found in infected human patients making them useful when studying protective immunity and latent M. tuberculosis infection.

Detailed description

Mice homozygous for the Il10^tm1Cgn 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. 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. 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.

Specifically, Il10-deficient mice on this CBA/J congenic background are relatively susceptible to Mycobacterium tuberculosis infection and are capable of forming mature, fibrotic M. tuberculosis-containing protective pulmonary granulomas similar to those found in infected human patients. This strain is useful when studying protective immunity and latent M. tuberculosis infection. Colitis has not been seen in these mice, but can develop systemic inflammation if stressed.

Of note, this Il10-deficient allele is also available on other defined genetic backgrounds including C3H/HeJBir (Stock No. 004326 and Stock No. 003968), 129/Sv (Stock No. 004368), BALB/cJ (Stock No. 004333), NOD/Lt (Stock No. 004266), C57BL/10 (Stock No. 002250), and C57BL/6J (Stock No. 002251). The onset and severity of both spontaneous and experimentally-induced inflammatory phenotype of Il10-deficient mice may be strongly influenced by the genetic background and the husbandry conditions (specific health status/commensal flora) of the vivaria in which mice are maintained.

Development

The Il10^tm1Cgn 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 Stock No. 002251. Some of these mice were subsequently backcrossed to CBA/J mice (Stock No. 000656) for 8 generations in the laboratory of Dr. Joanne Turner (Texas Biomedical Research Institute). These mice were shipped back to The Jackson Laboratory as this new Stock No. 036145. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize CBA/J oocytes.

Allele

Symbol: Il10^tm1Cgn
Name: targeted mutation 1, University of Cologne
MGI accession ID: MGI:1857199
Generation method: Targeted
Attributes: Null/Knockout
Synonyms: IL-10-; Il10-; IL-10 KO; IL-10^KO; Il10^tmCgn; IL-10KO
Marker symbol: Il10
Marker name: interleukin 10
Marker synonyms: CSIF; cytokine synthesis inhibitory factor; GVHDS; If2a; IL-10; IL10A; IL10X; TGIF
Chromosome: 1
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.