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Strain Name:

NOD.Cg-Rag1tm1Mom Cd86tm2Shr Cd80tm1Shr/JbsJ

Stock Number:

005273

Availability:

Repository-Cryopreserved


General Terms and Conditions

Former Name      NOD.Cg-Rag1tm1Mom Cd86tm2Shr/JbsJ    (Changed: 05-JAN-06 )
Genes & Alleles   Cd80;   Cd80tm1Shr;   Cd86;   Cd86tm2Shr;   Rag1;   Rag1tm1Mom;


Product Information

Strain Details

Type JAX® GEMM® Strain - Congenic
Additional information on JAX® GEMM® Strains.
Type JAX® GEMM® Strain - Mutant Strain
Type JAX® GEMM® Strain - Targeted Mutation
Specieslaboratory mouse
Background Strain NOD
Donor Strain 129/S4 (J1 ES cell)
Donating Investigator Jeffrey Bluestone,   University of California, San Francisco
GenerationN10F?+F6p

Strain Description
Mice homozygous for the Cd80tm1Shr and Cd86tm2Shr mutations are deficient in both CD80 and CD86. NOD mice defiecient for CD80, CD86 and Rag1 are viable and fertile, fail to produce T or B cells, and exhibit no signs of diabetes due to the absence of lymphocytes.
In an immunocompetent NOD background, the Cd86tm2Shr and Cd80tm1Shr mutations exacerbate diabetes onset as well as a variety of other autoimmune diseases including thyroiditis, sialitis, exocrine pancreas disease and neuropathy when compared to normal NOD controls. These mice have also been observed, by the donating investigator, to be Treg-deficient.
NOD.129(B6)-Rag1tm1Mom Cd86tm2ShrCd80tm1Shr/JbsJ are valuable for unraveling the co-stimulatory pathways of T cell activation and Treg function as they relate to autoimmune diseases and organ transplantation.

Strain Development
A targeting vector containing a hygromycin resistance gene under the control of the mouse phosphoglycerol kinase (PGK) promoter was used to disrupt the second Cd86 exon containing the Ig-V-like domain in J1 embryonic stem (ES) cells that were already heterozygous for a disruption in the Cd80 gene. ES cells were injected in to C57BL/6J blastocysts. This mutation was maintained on C57BL/6J prior to backcrossing to NOD and NOD-Rag1tm1Mom for 10 generations. In 2005,The Type 1 Diabetes Resource recieved NOD.Cg-Rag1tm1MomCd86tm2ShrCd80tm1Shr/JbsJ homozygous for all 3 targeted mutations at generation N10F?.

August 2008, informed by the donating investigator that they recently learned that this strain contains Rag2tm1Fwa allele and not the Rag1 tm1Mon allele. Genotyping for the Rag2tm1Fwa allele as follows:RAG-2-F 5'-gtgttgtcccctagagagac-3' NEO-R 5'-cgtcctgcagttcattcagg-3' RAG-2-R 5'-attgccagaaacgataccgt-3'. 94C-3min, repeat 35X-(94C- 30sec, 55C-55min, 72C-30sec). 72C-2min, 10C-hold. Wildtype band 260bp, heterozygous 260bp and 500bp and KO homozygous 500bp.

Gene & Allele Details

Allele Symbol Cd80tm1Shr
Allele Name targeted mutation 1, Arlene H Sharpe
Common Name(s) B7-; B7-1-; B7.1; CD80-;
Mutation Made By Arlene Sharpe,   Brigham and Women's Hospital
Strain of Origin129S4/SvJae
ES Cell Line NameJ1
ES Cell Line Strain129S4/SvJae
Gene Symbol and Name Cd80, CD80 antigen
Chromosome 16
Gene Common Name(s) B7-1; B7.1; CD28 antigen ligand; CD28LG; CD28LG1; Cd28l; LAB7; Ly-53; Ly53; lymphocyte antigen 53;
Molecular Note A neomycin selection cassette replaced the exon encoding the IgV-like domain of the protein. RT-PCR analysis on RNA derived from spleen, thymus and LPS-stimulated B cells of homozygous mice demonstrated that no detectable transcript was produced from this allele. FACS analysis on B cells derived from homozygous mice confirmed that no functional protein was encoded by this allele. [MGI Ref ID J:74662]
 
Allele Symbol Cd86tm2Shr
Allele Name targeted mutation 2, Arlene H Sharpe
Common Name(s) B7-1/2-; B7-1/B7-2-; B7.1/B7.2-; B7KO; Cd80/86-;
Mutation Made By Arlene Sharpe,   Brigham and Women's Hospital
Strain of Origin129S4/SvJae
ES Cell Line NameJ1
ES Cell Line Strain129S4/SvJae
Gene Symbol and Name Cd86, CD86 antigen
Chromosome 16
Gene Common Name(s) B7-2; B7.2; B70; CD28 antigen ligand; CD28LG2; Cd28l2; LAB72; Ly-58; Ly58; MB7-2; MGC34413; lymphocyte antigen 58;
Molecular Note To create a knockout of both Cd80 and Cd86 in mice, an ES cell line in which the Cd80 gene was mutated was subsequently used in a second round of gene targeting. A hygromycin selection cassette replaced an exon encoding the IgV-like domain of the protein and flanking genomic sequences of the Cd86 gene. FACS analysis on splenocytes and LPS-stimulated B cells derived from homozygous mice confirmed that no functional protein was encoded by this allele. [MGI Ref ID J:39089]
 
Allele Symbol Rag1tm1Mom
Allele Name targeted mutation 1, Peter Mombaerts
Common Name(s) RAG-1-; RAG1null; Rag-; Rag-1KO; Rag1-;
Mutation Made By Peter Mombaerts,   Max Planck Institute of Biophysics
Strain of Origin129S7/SvEvBrd-Hprt1<+>
ES Cell Line NameAB1
ES Cell Line Strain129S7/SvEvBrd-Hprt1<+>
Gene Symbol and Name Rag1, recombination activating gene 1
Chromosome 2
Gene Common Name(s) MGC43321; RNF74; Rag-1;
Molecular Note A 1356 bp genomic fragment of the Rag1 gene, encoding the nuclear localization signal and the zinc-finger motif, was replaced by a neomycin cassette. A mutant transcript expressed from this allele was detected by Northern blot in bone marrow derived cell lines from homozygous mice. [MGI Ref ID J:1934] [MGI Ref ID J:96036]

Control Information

  Control
   None Available
 
  Considerations for Choosing Controls

Genotyping Protocols

Cd80tm1Shr
Prkdcscid
Rag1tm1Mom

Colony Maintenance

Breeding & HusbandryThese mice are immunodeficient and need to be maintained in a high barrier environment with sterile food, water and cage.

Related Strains

Strains carrying   Cd80tm1Shr allele
003610   B6.129S4-Cd80tm1Shr Cd86tm2Shr/J
003611   B6.129S4-Cd80tm1Shr/J
004673   NOD.129(B6)-Rag1tm1Mom Cd80tm1Shr/JbsJ
View Strains carrying   Cd80tm1Shr     (3 strains)

Strains carrying   Cd86tm2Shr allele
003610   B6.129S4-Cd80tm1Shr Cd86tm2Shr/J
View Strains carrying   Cd86tm2Shr     (1 strain)

View Strains carrying   Rag1tm1Mom     (16 strains)

Strains carrying other alleles of Cd80
007769   NOD.FVB-Tg(Igh-6-Cd80)1Gjf/JbsJ
006778   NOD/ShiLt-Tg(GFAP-Cd80)9Mdos/MdosJ
View Strains carrying other alleles of Cd80     (2 strains)

Strains carrying other alleles of Cd86
003609   B6.129S4-Cd86tm1Shr/J
004762   NOD.129S4-Cd86tm1Shr/JbsJ
View Strains carrying other alleles of Cd86     (2 strains)

Strains carrying other alleles of Rag1
002194   B6;CBA-Tg(CD3E)26Cpt/J
002506   STOCK Tg(CD3E)26Cpt-Rag1tm1Mom/J
View Strains carrying other alleles of Rag1     (2 strains)

Additional Web Information

Congenic Nomenclature

Research Applications

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

Diabetes and Obesity Research
Type 1 Diabetes (IDDM)

Immunology and Inflammation Research
Autoimmunity (Type 1 Diabetes)

Cd80tm1Shr related

Immunology and Inflammation Research
CD Antigens, Antigen Receptors, and Histocompatibility Markers
Immunodeficiency Associated with Other Defects
Intracellular Signaling Molecules
Lymphoid Tissue Defects

Internal/Organ Research
Lymphoid Tissue Defects

Rag1tm1Mom related

Cancer Research
Toxicology (B and T cell deficiency) (xenograft/transplant host)

Hematological Research
Immunological Defects (B and T cell deficiency)

Immunology and Inflammation Research
Immunodeficiency (B and T cell deficiency)
Inflammation (B and T cell deficiency)
T Cell Receptor Signaling Defects (B and T cell deficiency)

Internal/Organ Research
Lymphoid Tissue Defects (B and T cell deficiency)

Research Tools
Cancer Research (B and T cell deficiency) (xenograft/transplant host)
Toxicology Research (xenograft/transplant host)

References

Selected Reference(s)

Borriello F; Sethna MP; Boyd SD; Schweitzer AN; Tivol EA; Jacoby D ; Strom TB ; Simpson EM ; Freeman GJ ; Sharpe AH. 1997. B7-1 and B7-2 have overlapping, critical roles in immunoglobulin class switching and germinal center formation. Immunity 6(3):303-13. [PubMed: 9075931]  [MGI Ref ID J:39089]

Additional References

Price and Supply Information

Strain Name: NOD.Cg-Rag1tm1Mom Cd86tm2Shr Cd80tm1Shr/JbsJ
Stock Number: 005273

Price Details

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Supply Details

Standard SupplyRepository-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; Email: jaxservices@jax.org.
This strain is included in the Type 1 Diabetes Repository collection.

LicensingSee General Terms and Conditions below for Licensing and Use Restrictions  
Control InformationView Control Information in Strain Details.

General Terms and Conditions

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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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