Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse   Donating Investigator Sherman Fong,   Genentech, Inc.

Description
Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No gene product (mRNA) is detected by Northern blot analysis of ES cells. After 12 weeks of age, approximately 60% of mutant mice develop chronic colitis and increased numbers of splenocytes resulting in splenomegaly. Bone marrow-derived macrophages, splenocytes and peritoneal cells derived from homozygotes do not respond to IL-10. Mutant mice housed in non-SPF conditions do not breed well. This mutant mouse strain may be useful in studies of the role of interleukin-10 in inflammatory diseases such as chronic colitis.

Development
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt exons 1 and 2, which encode the signal peptide and the first 39 amino acids. The construct was electroporated into 129S2/SvPas-derived D3 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts.

Additional Web Information

Congenic Nomenclature
Genetic Quality Control Annual Report

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms

Inflammatory Bowel Disease 11; IBD11 - Models with phenotypic similarity to human disease where etiologies are distinct.2

2 Human genes are associated with this disease. Orthologs of those genes do not appear in the mouse genotype(s).

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Il10rb^tm1Agt/Il10rb^tm1Agt

        involves: 129S2/SvPas * C57BL/6

• immune system phenotype
• abnormal granulocyte differentiation (MGI Ref ID J:45917)
  • increased granulocytopoiesis in sternal bone marrow
• abnormal lymph node medulla (MGI Ref ID J:45917)
  • increased number of plasma cells in the medullary cords of mesenteric lymph nodes
• abnormal mesenteric lymph node morphology (MGI Ref ID J:45917)
  • mesenteric lymphadenopathy
• abnormal spleen morphology (MGI Ref ID J:45917)
• increased spleen weight (MGI Ref ID J:45917)
  • 4 fold increase in the spleen/body weight ratio
• spleen hyperplasia (MGI Ref ID J:45917)
  • increased numbers of splenocytes
• increased interferon-gamma secretion (MGI Ref ID J:134156)
  • there is an increase in the percentage of CD8 T cells producing IFN-gamma compared to wild-type mice
• increased interleukin-17 secretion (MGI Ref ID J:134156)
  • there is an increased percentage of CD4 T cells producing IL-17 in the mesenteric lymph nodes and the lamina propria of 4-5 week old mice
• increased leukocyte cell number (MGI Ref ID J:45917)
  • peripheral leukocytosis involving neutrophiles and monocytes
• large intestinal inflammation (MGI Ref ID J:45917)
  • mixed inflammatory cell mucosal inflammation in the large intestine
  • predominantly involves macrophage, neutrophiles and T lymphocytes
• colitis (MGI Ref ID J:134156)
  • colitis is observed in mice 3-4 months of age with ulcerations found near the iliel-cecal junction, the ascending-to-descending colon transition and the anal-rectal junction
• hematopoietic system phenotype
• abnormal granulocyte differentiation (MGI Ref ID J:45917)
  • increased granulocytopoiesis in sternal bone marrow
• abnormal spleen morphology (MGI Ref ID J:45917)
• increased spleen weight (MGI Ref ID J:45917)
  • 4 fold increase in the spleen/body weight ratio
• spleen hyperplasia (MGI Ref ID J:45917)
  • increased numbers of splenocytes
• decreased hemoglobin content (MGI Ref ID J:45917)
  • decreased peripheral hemoglobin
• extramedullary hematopoiesis (MGI Ref ID J:45917)
  • increased in the red pulp of the spleen
  • involves erythroid, myeloid, and megakaryocytic lineages
• increased leukocyte cell number (MGI Ref ID J:45917)
  • peripheral leukocytosis involving neutrophiles and monocytes
• digestive/alimentary phenotype
• abnormal crypts of Lieberkuhn morphology (MGI Ref ID J:45917)
  • occasional hyperplasia of crypt epithelium
• abnormal large intestine morphology (MGI Ref ID J:45917)
  • thickened and narrowed
• large intestinal inflammation (MGI Ref ID J:45917)
  • mixed inflammatory cell mucosal inflammation in the large intestine
  • predominantly involves macrophage, neutrophiles and T lymphocytes
• colitis (MGI Ref ID J:134156)
  • colitis is observed in mice 3-4 months of age with ulcerations found near the iliel-cecal junction, the ascending-to-descending colon transition and the anal-rectal junction
• endocrine/exocrine gland phenotype
• abnormal crypts of Lieberkuhn morphology (MGI Ref ID J:45917)
  • occasional hyperplasia of crypt epithelium

View Research Applications

Research Applications

This mouse can be used to support research in many areas including:

Il10rb^tm1Agt related

Immunology and Inflammation Research
Inflammation (Inflammatory bowel disease)
Lymphoid Tissue Defects

Internal/Organ Research
Spleen Defects

Genes & Alleles

Gene & Allele Information

Allele Symbol		Il10rbtm1Agt
Allele Name		Targeted mutation 1, Michael Aguet
Allele Type		Targeted (knock-out)
Common Name(s)		CRFB4-; IL-10-;
Mutation Made By		Sherman Fong,   Genentech, Inc.
Strain of Origin		129S2/SvPas
ES Cell Line Name		D3
ES Cell Line Strain		129S2/SvPas
Gene Symbol and Name		Il10rb, interleukin 10 receptor, beta
Chromosome		16
Gene Common Name(s)		6620401D04Rik; AI528744; CDW210B; CRF2-4; CRFB4; Crfb4; D16H21S58; D21S58; D21S58h; D21S66; DNA segment, Chr 16, human D21S58; IL-10R2; Il10r2; RGD1560373; RIKEN cDNA 6620401D04 gene; cytokine receptor family 2, member 4; expressed sequence AI528744;
Molecular Note		The first two exons, encoding 39 amino acids including the signal peptide, were replaced with a neomycin cassette. Northern blot analysis of homozygous mutant ES cells showed an absence of transcript. [MGI Ref ID J:45917]

Genotyping

Genotyping Information

Genotyping Protocols

Il10rb^tm1Agt, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Spencer SD; Di Marco F; Hooley J; Pitts-Meek S; Bauer M; Ryan AM; Sordat B; Gibbs VC; Aguet M. 1998. The orphan receptor CRF2-4 is an essential subunit of the interleukin 10 receptor. J Exp Med 187(4):571-8. [PubMed: 9463407]  [MGI Ref ID J:45917]

Additional References

Il10rb^tm1Agt related

Gu Y; Yang J; Ouyang X; Liu W; Li H; Yang J; Bromberg J; Chen SH; Mayer L; Unkeless JC; Xiong H. 2008. Interleukin 10 suppresses Th17 cytokines secreted by macrophages and T cells. Eur J Immunol 38(7):1807-13. [PubMed: 18506885]  [MGI Ref ID J:137290]

Huang B; Pan PY; Li Q; Sato AI; Levy DE; Bromberg J; Divino CM; Chen SH. 2006. Gr-1+CD115+ immature myeloid suppressor cells mediate the development of tumor-induced T regulatory cells and T-cell anergy in tumor-bearing host. Cancer Res 66(2):1123-31. [PubMed: 16424049]  [MGI Ref ID J:106544]

Kang SS; Allen PM. 2005. Priming in the presence of IL-10 results in direct enhancement of CD8+ T cell primary responses and inhibition of secondary responses. J Immunol 174(9):5382-9. [PubMed: 15843536]  [MGI Ref ID J:98415]

Kang SS; Bloom SM; Norian LA; Geske MJ; Flavell RA; Stappenbeck TS; Allen PM. 2008. An antibiotic-responsive mouse model of fulminant ulcerative colitis. PLoS Med 5(3):e41. [PubMed: 18318596]  [MGI Ref ID J:134156]

Spach KM; Nashold FE; Dittel BN; Hayes CE. 2006. IL-10 signaling is essential for 1,25-dihydroxyvitamin D3-mediated inhibition of experimental autoimmune encephalomyelitis. J Immunol 177(9):6030-7. [PubMed: 17056528]  [MGI Ref ID J:140527]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Breeding & Husbandry	The resulting male chimeric animals were crossed to C57BL/6 female mice, and then backcrossed to C57BL/6J mice for 6 generations using a speed congenic protocol.

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.

Supply Notes

Cryopreserved Embryos This strain is also available as cryopreserved embryos from our Repository. Orders for cryopreserved embryos are supplied subject to a signed agreement that must be returned to the Customer Service Department after order placement. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos from our repository, please visit our Cryopreserved Embryos web page. Cryorecovery - Standard. The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845. This strain is included in the Induced Mutant Resource Colony collection. Genomic DNA is available for this strain from the Mouse DNA Resource.

General Terms and Conditions

See Terms of Use

The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX^® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX^® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX^® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.

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Ordering and Purchasing Information

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Contact Information
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Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
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Terms of Use

Terms of Use

General Terms and Conditions

Contact information

General inquiries

Contracts Administration

phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (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 with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of MICE, products or services, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.

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In no event shall The Jackson Laboratory, 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 The Jackson Laboratory, its agents or employees. In purchasing or receiving MICE, products or services from The Jackson Laboratory, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges The Jackson Laboratory from all such causes of action or damages, and further agrees to defend and indemnify The Jackson Laboratory from any costs or damages arising out of any third party claims.

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The foregoing represents the General Terms and Conditions applicable to The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory 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 The Jackson Laboratory, 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 The Jackson Laboratory, 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 services by The Jackson Laboratory.