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Strain Name:

B6.129S4-Cd80tm1Shr Cd86tm2Shr/J

Stock Number:

003610

Availability:

Repository- Live

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Former Name      B6.129S4-Cd80tm1Shr Cd86tm1Shr/J    (Changed: 06-DEC-06 )
Genes & Alleles   Cd80;   Cd80tm1Shr;   Cd86;   Cd86tm2Shr;

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
Mating SystemHomozygote x Homozygote         (Female x Male)
Specieslaboratory mouse
Background Strain C57BL/6
Donor Strain 129 derived ES cell line
Donating Investigator Arlene Sharpe,   Brigham and Women's Hospital
GenerationN10F?+17 (20-DEC-06)

Strain Description
Cd80/Cd86-mediated signaling is critical to germinal center formation and Ig class switching in vivo. Mice homozygous for both the Cd80 (B7-1) and Cd86 (B7-2) targeted mutations are viable, fertile and have a normal life span. Homozygous null Cd80/Cd86 mice fail to generate antigen specific IgG1 and IgG2a responses. During the postimmunization period (7-10 days) they have smaller spleens devoid of germinal centers. Unimmunized null mice exhibit a 3-to-5 fold reduction in total serum immunoglobulin and IgG2a. Levels of IgG1 are also reduced 5-10 fold. Levels of IgM and IgG3 are elevated 3-5 fold. When immunized, antigen specific IgG1 and IgG2a isotype levels are 0.1% that of wild type levels. Levels remain low even when immunization is performed with adjuvent. This strain is also resistant to myelin oligodendrocyte glycoprotein (MOG) 35-55 peptide-induced experimental autoimmune encephalomyelitis (EAE), a T cell-mediated autoimmune disease that shares some features with multiple sclerosis (MS). These mice have been used to delineate the roles of CD80 and CD86, along with CD28 and CTLA-4, in the activation and differentiation of CD4+ T helper cells and CD8+ T cytotoxic cells.

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.

Mammalian Phenotype Terms assigned by genotype

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

Cd80tm1Shr/Cd80tm1Shr Cd86tm2Shr/Cd86tm2Shr

        involves: 129S4/SvJae
  • hematopoietic system phenotype
  • abnormal T cell proliferation (MGI Ref ID J:57090)
    • during primary response after antigen stimulation, T cells produce less than cells that are additionally Ctla4-null
  • abnormal spleen morphology (MGI Ref ID J:39089)
    • after immunization with complete Freund's adjuvant, spleens examined 7-10 days later were significantly smaller than wild type
  • immune system phenotype
  • abnormal T cell physiology (MGI Ref ID J:57090)
    • cells secrete more interferon gamma and less Il-4 than Ctla4-null cells
    • abnormal T cell proliferation (MGI Ref ID J:57090)
      • during primary response after antigen stimulation, T cells produce less than cells that are additionally Ctla4-null
  • abnormal lymph node B cell domain (MGI Ref ID J:39089)
    • lymphoid follicles are small, resembling primary follicles without recognizable germinal centers
  • abnormal spleen morphology (MGI Ref ID J:39089)
    • after immunization with complete Freund's adjuvant, spleens examined 7-10 days later were significantly smaller than wild type
  • decreased IgG level (MGI Ref ID J:39089)
    • unimmunized mice show a 2 to 5-fold reduction in total serum IgG and IgG2a and a 5 to 10-fold reduction in IgG1
    • decreased IgG1 level (MGI Ref ID J:39089)
    • decreased IgG2a level (MGI Ref ID J:39089)
  • increased IgG3 level (MGI Ref ID J:39089)
    • mutants have a 3 to 5-fold elevation in IgG3
  • increased IgM level (MGI Ref ID J:39089)
    • mutants have a 3 to 5-fold elevation in IgM

Cd80tm1Shr/Cd80tm1Shr Cd86tm2Shr/Cd86tm2Shr

        129.SJL-Cd86tm2Shr
  • cellular phenotype
  • decreased cell proliferation (MGI Ref ID J:78992)
    • proliferative responses of lymph node cells to myelin proteolipid protein peptide 139-151 or 178-191 are impaired in null mice compared to wild-type
  • immune system phenotype
  • decreased interleukin-2 secretion (MGI Ref ID J:78992)
    • no IL-2 production could be detected in draining lymph node cells
  • decreased susceptibility to experimental autoimmune encephalomyelitis (MGI Ref ID J:78992)
    • mice develop EAE, but severity is lower and time of onset is delayed compared to wild-type SJL mice
  • increased susceptibility to experimental autoimmune encephalomyelitis (MGI Ref ID J:78992)
    • null mice on a 129 background are susceptible to EAE, whereas nulls on a B6 background are resistant
  • nervous system phenotype
  • abnormal meninges (MGI Ref ID J:78992)
    • in mice exhibiting EAE, there are lesions in the meniges and parenchyma of the spinal cord and brain; number of lesions is lower than in wild-type mice with EAE
    • lesions associated with white matter vacuolation occur with higher incidence in null mice compared to wild-type mice with EAE

Cd80tm1Shr/Cd80tm1Shr Cd86tm2Shr/Cd86tm2Shr

        involves: 129S4/SvJae * C57BL/6J * SJL
  • cellular phenotype
  • decreased cell proliferation (MGI Ref ID J:78992)
    • lymph node cells from null animals proliferate poorly compared to wild type, but do produce IFNG in response to PLP or MOG peptides
  • immune system phenotype
  • decreased susceptibility to experimental autoimmune encephalomyelitis (MGI Ref ID J:78992)
    • null mice on the mixed background are resistant to EAE when immunized with either PLP 139-151 or myelin oligodendrocyte glycoprotein 35-55 compared with wild type (B6 x SJL)F1 mice
  • nervous system phenotype
  • abnormal meninges (MGI Ref ID J:78992)
    • numbers of foci in the meninges and parenchyma of the spinal cords of null mice are lower compared to control mice

Cd80tm1Shr/Cd80tm1Shr Cd86tm2Shr/Cd86tm2Shr

        involves: 129S4/SvJae * BALB/c
  • hematopoietic system phenotype
  • abnormal T cell number (MGI Ref ID J:112266)
    • mice have increased CD4/CD8 ratios in the spleen (4.1 vs 2.2 in controls) and in lymph nodes (6.6 vs 2.8 in controls), reciprocal to the decreased ratios seen in transgenic Cd86 or Cd80 mice
    • decreased double-positive T cell number (MGI Ref ID J:112266)
      • ther are fewer double positive cells (74.3%) compared to controls (83.8%) and higher CD4+ cell numbers (17.2% vs 10.5%)
  • immune system phenotype
  • abnormal T cell number (MGI Ref ID J:112266)
    • mice have increased CD4/CD8 ratios in the spleen (4.1 vs 2.2 in controls) and in lymph nodes (6.6 vs 2.8 in controls), reciprocal to the decreased ratios seen in transgenic Cd86 or Cd80 mice
    • decreased double-positive T cell number (MGI Ref ID J:112266)
      • ther are fewer double positive cells (74.3%) compared to controls (83.8%) and higher CD4+ cell numbers (17.2% vs 10.5%)

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]

Control Information

  Control
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Genotyping Protocols

Cd80tm1Shr

Colony Maintenance

Breeding & HusbandryThis strain originated on a B6/129S4 background. It was backcrossed to B6 for ten generations and has been maintained with intercrosses since N10. It is maintained as a homozygote. Coat color expected from breeding:Black
Diet Information LabDiet® 5K52/5K67

Related Strains

Strains carrying   Cd80tm1Shr allele
003611   B6.129S4-Cd80tm1Shr/J
004673   NOD.129(B6)-Rag1tm1Mom Cd80tm1Shr/JbsJ
005273   NOD.Cg-Rag1tm1Mom Cd86tm2Shr Cd80tm1Shr/JbsJ
View Strains carrying   Cd80tm1Shr     (3 strains)

Strains carrying   Cd86tm2Shr allele
005273   NOD.Cg-Rag1tm1Mom Cd86tm2Shr Cd80tm1Shr/JbsJ
View Strains carrying   Cd86tm2Shr     (1 strain)

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)

Additional Web Information

Congenic Nomenclature
Genetic Quality Control Annual Report

Animal Health Reports

Room Number           AX12

Research Applications

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

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

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: B6.129S4-Cd80tm1Shr Cd86tm2Shr/J
Stock Number: 003610

Price Details

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Supply Details

Standard SupplyRepository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement.
Supply Notes Usually shipped between four and eight weeks of age.
This strain is included in the Induced Mutant Resource Colony collection.
Genomic DNA is available for this strain from the Mouse DNA Resource.
LicensingSee General Terms and Conditions below for Licensing and Use Restrictions  
Control InformationView Control Information in Strain Details.

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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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