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Strain Name:

NOD.Cg-Rag1tm1Mom H2-Ab1tm1Gru Tg(CD2-CD4,HLA-DQA1,HLA-DQB1)1Ell/EllJ

Stock Number:

006022

Availability:

Repository-Cryopreserved

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Former Name      NOD.Cg-Rag1tm1Mom H2-Ab1tm1Gru Tg(CD2-CD4,HLA-DQA1*0301,HLA-DQB1*0302)1Ell/EllJ    (Changed: 23-AUG-06 )
Genes & Alleles   CD2;   CD4;   H2-Ab1;   H2-Ab1tm1Gru;   HLA-DQA1;   HLA-DQB1;   Rag1;   Rag1tm1Mom;   Tg(CD2-CD4,HLA-DQA1,HLA-DQB1)1Ell;

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
Type JAX® GEMM® Strain - Transgenic
Specieslaboratory mouse
Background Strain NOD
Donor Strain 129
Donating Investigator John Elliott,   University of Alberta
H2 Haplotypeg7
Generation?+F2p

Appearance
pink-eyed, albino
Related Genotype: A/A Tyrc/Tyrc

Strain Description
Rag1 and H2-Ab1 deficient NOD mice carrying transgenes coding for human CD2-CD4 and HLA-DQ8 lack T and B cells, and are diabetes free. Also, unlike the H2-Ab1 deficient, transgenic CD4, HLA-DQ8 mice (see Stock No. 006621), this strain does not develop cardiomyopathy.

This model is useful in adoptive transfer experiments and to understand the role of MHC class II in autoimmunity.

Strain Development
Congenic, H2-Ab1 deficient, NOD mice carrying transgenes coding for CD2-CD4 and DQ8(Stock No. 006021) were crossed to NOD congenic Rag1 deficient mice (Stock No. 003729) and were bred to homozygosity for the H2-Ab1tm1Gru and Rag1tm1Mom targeted mutations. The T1DR received NOD.Cg-Rag1tm1Mom H2-Ab1tm1Gru Tg(CD2-CD4,HLA-DQA1,HLA-DQB1)1Ell/EllJ in 2006.

Mammalian Phenotype Terms assigned by genotype

H2-Ab1tm1Gru/H2-Ab1tm1Gru Rag1tm1Mom/Rag1tm1Mom Tg(CD2-CD4,HLA-DQA1,HLA-DQB1)1Ell/Tg(CD2-CD4,HLA-DQA1,HLA-DQB1)1Ell

        NOD.Cg-Rag1tm1Mom H2-Ab1tm1Gru Tg(CD2-CD4,HLA-DQA1,HLA-DQB1)1Ell
  • cardiovascular system phenotype
  • *normal* cardiovascular system phenotype (MGI Ref ID J:113267)
    • animals have normal sized hearts, normal ECG, and show no sign of autoimmune pathology
    • abnormal PQ interval (MGI Ref ID J:113267)
      • mice receiving splenic lymphocytes from animals with heart block display first-degree heart block as early as 2 weeks after transfer, with 50% progressing to complete heart block in 8 weeks
    • enlarged heart (MGI Ref ID J:113267)
      • recipient animals develop cardiomegaly by 12 weeks after transfer
    • heart inflammation (MGI Ref ID J:113267)
      • recipient animals develop mononuclear cell infiltrates within heart wall by 12 weeks after transplant
      • myocarditis (MGI Ref ID J:113267)
        • when young mice receive splenic lymphocytes from older NOD.DQ8/H2Ab-1 mice with heart block, myocarditis is triggered in 100% of recipients
  • immune system phenotype
  • abnormal response to transplant (MGI Ref ID J:113267)
    • younger mice receiving splenic lymphocytes from older DQ8 transgenic, H2-Ab1-null mice with heart block develop heart block, myocarditis, and autoantibodies
    • when younger mice receive serum from the same older animals, no cardiac pathology is observed
    • recipient mice receiving CD4 T cells from older donor animals with heart block develop heart block as early as 4 weeks posttransfer; all animals are diseased by 12 weeks and upon necropsy, heart are enlarged
    • mononuclear cells are more numerous and infiltrates more widespread than in animals that receive total splenocytes (containing CD4 T cells) in the myocardium
    • disease onset is somewhat accelerated compared to recipients receiving total lymphocytes;
  • heart inflammation (MGI Ref ID J:113267)
    • recipient animals develop mononuclear cell infiltrates within heart wall by 12 weeks after transplant
    • myocarditis (MGI Ref ID J:113267)
      • when young mice receive splenic lymphocytes from older NOD.DQ8/H2Ab-1 mice with heart block, myocarditis is triggered in 100% of recipients
  • increased autoantibody level (MGI Ref ID J:113267)
    • anticardiac myosin autoantibodies reach a titer of 1:10000 in recipient mice at 12 weeks posttransfer

Gene & Allele Details

Allele Symbol H2-Ab1tm1Gru
Allele Name targeted mutation 1, Michael J Grusby
Common Name(s) Ab1tm1Gru; Abb-; Abbtm1; Abeta-; Abetab-; C2-; H2-Ab1-; H2-Ab1tm1Glm; I-Ab-; I-Abetab-; IAb-; IAbeta-; MHC class II-; [KO]Abb; mII-;
Mutation Made By Michael Grusby,   Harvard Medical School
Strain of Origin129S2/SvPas
ES Cell Line NameD3
ES Cell Line Strain129S2/SvPas
Gene Symbol and Name H2-Ab1, histocompatibility 2, class II antigen A, beta 1
Chromosome 17
Gene Common Name(s) A beta; AI845868; Abeta; CELIAC1; H-2Ab; H2-Ab; HLA-DQB; I-Ab; I-Abeta; I-region-associated antigen 2; IAb; IDDM1; Ia-2; Ia2; Rmcs1; expressed sequence AI845868; histocompatibility 2, class II antigen A, beta; response to metastatic cancers 1;
Molecular Note A neomycin selection cassette was inserted into exon 2. In addition, the ES cell line used was derived from the 129S2/SvPas strain, which carries a deletion in the promoter region of H2-Ea. Consequently, these MHC class II molecule-deficient mice lacked cell surface expression of both class II-A and class II-E MHC proteins. [MGI Ref ID J:74418]
 
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]
 
Allele Symbol Tg(CD2-CD4,HLA-DQA1,HLA-DQB1)1Ell
Allele Name transgene insertion 1, John F Elliott
Common Name(s) DQ8+; Tg(CD2-CD4,HLA-DQA1*0301,HLA-DQB1*0302)1Ell; Tg(CD4,HLA-DQ8)1Ell; human CD4, DQ8 transgene; human CD4, DQA1*0301, DQB1*0302 transgene;
Strain of OriginNOD/MrkTac
Expressed Gene HLA-DQA1, major histocompatibility complex, class II, DQ alpha 1, human
Expressed Gene CD4, CD4 molecule, human
Expressed Gene HLA-DQB1, major histocompatibility complex, class II, DQ beta 1, human
Promoter HLA-DQA1, major histocompatibility complex, class II, DQ alpha 1, human
Promoter CD2, CD2 molecule, human
Promoter HLA-DQB1, major histocompatibility complex, class II, DQ beta 1, human
General Note Although in NOD mice homozygous for this transgene alone endogeous NOD H2-Abetag7 and transgene-derived HLA-DQ8 are expressed at similar levels, virtually all CD4+ T-cell responses are H2Abeta1g7 restricted (J:87013).
Molecular Note Fertilized oocytes were co-injected with two DNA fragments: a human CD4 cDNA joined to the promoter from the human CD2 gene and a large DNA fragment, reassembled from segments of the cosmid pDCbeta2, containing the human major histocompatibility (MHC) class II alleles HLA-DQA1*0301 and HLA-DQB*0302, which together encode the dimer comprising the HLA-DQ8 molecule, plus 5' regulatory elements. Human CD4 is expressed at a low level on all T cells of transgenic mice. HLA-DQ8 is expressed in homozygous NOD mice at a level comparable to that of the endogenous NOD H2-Abetag7 MHC class II molecule in wild type NOD mice. [MGI Ref ID J:113267] [MGI Ref ID J:87013]

Control Information

  Control
   003729 NOD.129S7(B6)-Rag1tm1Mom/J
   001976 NOD/ShiLtJ
 
  Considerations for Choosing Controls

Genotyping Protocols

H2-Ab1tm1Gru
Rag1tm1Mom
Tg(CD2-CD4,HLA-DQA1,HLA-DQB1)1Ell

Colony Maintenance

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

Related Strains

View Strains carrying   H2-Ab1tm1Gru     (5 strains)

View Strains carrying   Rag1tm1Mom     (16 strains)

Strains carrying   Tg(CD2-CD4,HLA-DQA1,HLA-DQB1)1Ell allele
006021   NOD.Cg-H2-Ab1tm1Gru Tg(CD2-CD4,HLA-DQA1,HLA-DQB1)1Ell/EllJ
View Strains carrying   Tg(CD2-CD4,HLA-DQA1,HLA-DQB1)1Ell     (1 strain)

Strains carrying other alleles of CD2
003331   C57BL/6-Tg(Cd8aCd8b)3Erob/J
View Strains carrying other alleles of CD2     (1 strain)

View Strains carrying other alleles of CD4     (2 strains)

View Strains carrying other alleles of H2-Ab1     (6 strains)

View Strains carrying other alleles of HLA-DQA1     (3 strains)

View Strains carrying other alleles of HLA-DQB1     (3 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) Analysis Strains (NOD Congenics with Mutations Affecting Immunocompetence)
Type 1 Diabetes (IDDM) Analysis Strains (NOD Transgenics)

Immunology and Inflammation Research
Immunodeficiency (MHC class II deficient)
Rearranged Antigen-Specific T Cell Receptor Transgenes (class II restricted)
T Cell Receptor Signaling Defects (B and T cell deficiency) (xenograft/transplant host)

Research Tools
Immunology and Inflammation Research (MHC class II defects)

H2-Ab1tm1Gru related

Immunology and Inflammation Research
CD Antigens, Antigen Receptors, and Histocompatibility Markers
Immunodeficiency

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)

Elliott JF; Liu J; Yuan ZN; Bautista-Lopez N; Wallbank SL; Suzuki K; Rayner D; Nation P; Robertson MA; Liu G; Kavanagh KM. 2003. Autoimmune cardiomyopathy and heart block develop spontaneously in HLA-DQ8 transgenic IAbeta knockout NOD mice. Proc Natl Acad Sci U S A 100(23):13447-52. [PubMed: 14570980]  [MGI Ref ID J:86540]

Liu J; Purdy LE; Rabinovitch S; Jevnikar AM; Elliott JF. 1999. Major DQ8-restricted T-cell epitopes for human GAD65 mapped using human CD4, DQA1*0301, DQB1*0302 transgenic IA(null) NOD mice. Diabetes 48(3):469-77. [PubMed: 10078545]  [MGI Ref ID J:87013]

Additional References

Price and Supply Information

Strain Name: NOD.Cg-Rag1tm1Mom H2-Ab1tm1Gru Tg(CD2-CD4,HLA-DQA1,HLA-DQB1)1Ell/EllJ
Stock Number: 006022

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 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.

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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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