Overview

Also Known As:NOD.DQ8, H2-Ab0^null,Rag1^null

These NOD mice carry human CD4 and HLA- DQ8 transgenes along with the Rag1^tm1Mom and Ab1^tm1Gru targeted mutations and are free from both autoimmune diabetes and cardiomyopathy.

Donating Investigator

John Elliott, University of Alberta

Genetic overview

Genetic Background	Generation

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

Allele Type
Transgenic (Inserted expressed sequence, Humanized sequence)

Rag1^tm1Mom

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Rag1	recombination activating gene 1

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	H2-Ab1	histocompatibility 2, class II antigen A, beta 1

Research Applications

Immunology, Inflammation and Autoimmunity Research
Research Tools
Diabetes and Obesity Research
Internal/Organ Research
Cancer Research
Hematological Research

View All Research Applications

Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

View Price List

Details

Detailed 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. 006021), 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.

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-Ab1^tm1Gru and Rag1^tm1Mom targeted mutations. The T1DR received NOD.Cg-Rag1^tm1Mom H2-Ab1^tm1Gru Tg(CD2-CD4,HLA-DQA1,HLA-DQB1)1Ell/EllJ in 2006.

Expression Data

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
Site of Expression
Site of Expression	expression is seen in bone marrow derived cell lines.
Site of Expression

Control Suggestions

Additional Information

Considerations for Choosing Controls

Selected References

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):13447-52PubMed: 14570980 MGI: 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):469-77PubMed: 10078545 MGI: J:87013

View All References

Genetics

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

Allele Symbol: Tg(CD2-CD4,HLA-DQA1,HLA-DQB1)1Ell

Allele Name	transgene insertion 1, John F Elliott
Allele Type	Transgenic (Inserted expressed sequence, Humanized sequence)
Allele Synonym(s)	DQ8⁺; human CD4, DQ8 transgene; human CD4, DQA10301, DQB10302 transgene; Tg(CD2-CD4,HLA-DQA10301,HLA-DQB10302)1Ell; Tg(CD4,HLA-DQ8)1Ell
Gene Symbol and Name	Tg(CD2-CD4,HLA-DQA1,HLA-DQB1)1Ell, transgene insertion 1, John F Elliott
Gene Synonym(s)
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
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
Strain of Origin	NOD/MrkTac
Chromosome	UN
General Note	Although in NOD mice homozygous for this transgene alone endogeous NOD H2-Abeta^g7 and transgene-derived HLA-DQ8 are expressed at similar levels, virtually all CD4⁺ T-cell responses are H2Abeta1^g7 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-DQA10301 and HLA-DQB0302, 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-Abeta^g7 MHC class II molecule in wild-type NOD mice.

Rag1^tm1Mom

Allele Symbol: Rag1^tm1Mom

Allele Name	targeted mutation 1, Peter Mombaerts
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	Rag-; Rag^1tm1Mom; RAG-1-; Rag1^-; RAG1^null; Rag-1KO
Gene Symbol and Name	Rag1, recombination activating gene 1
Gene Synonym(s)
Site of Expression	expression is seen in bone marrow derived cell lines.
Strain of Origin	129S7/SvEvBrd-Hprt⁺
Chromosome	2
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.
Mutations Made By	Peter Mombaerts, Max Planck Research Unit for Neurogenetics

H2-Ab1^tm1Gru

Allele Symbol: H2-Ab1^tm1Gru

Allele Name	targeted mutation 1, Michael J Grusby
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	[KO]Ab^b; A^bbeta^-; Ab1^tm1Gru; Abb-; Abb^tm1; Abeta-; Abeta^b-; C2-; H2-Ab1^-; H2-Ab1^tm1Glm; I-A^b-; IAb^-; IAbeta-; I-Abeta^b-; MHC class II-; MHC-II-deficient; mII^-
Gene Symbol and Name	H2-Ab1, histocompatibility 2, class II antigen A, beta 1
Gene Synonym(s)
Strain of Origin	129S2/SvPas
Chromosome	17
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.
Mutations Made By	Dr. Michael Grusby, Harvard Medical School

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Immunology, Inflammation and Autoimmunity Research
- T Cell Receptor Signaling Defects
  - B and T cell deficiency, xenograft/transplant host
- Immunodeficiency
  - MHC class II deficient
- HLA transgenics
Research Tools
- Immunology, Inflammation and Autoimmunity Research
  - MHC class II defects
Diabetes and Obesity Research
- Type 1 Diabetes (IDDM) Analysis Strains
  - NOD Congenics with Mutations Affecting Immunocompetence
  - NOD Transgenics

Genotype: Rag1^tm1Mom related

Immunology, Inflammation and Autoimmunity Research
- T Cell Receptor Signaling Defects
  - B and T cell deficiency
- Immunodeficiency
  - B and T cell deficiency
- Inflammation
  - B and T cell deficiency
Research Tools
- Toxicology Research
  - xenograft/transplant host
- Cancer Research
  - B and T cell deficiency, xenograft/transplant host
Internal/Organ Research
- Lymphoid Tissue Defects
  - B and T cell deficiency
Cancer Research
- Toxicology
  - B and T cell deficiency, xenograft/transplant host
Hematological Research
- Immunological Defects
  - B and T cell deficiency

Genotype: H2-Ab1^tm1Gru related

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

Mammalian Phenotype Terms by Genotype

The following phenotype relates to a compound genotype created using this strain

Genotype: H2-Ab1^tm1Gru/H2-Ab1^tm1Gru Rag1^tm1Mom/Rag1^tm1Mom Tg(CD2-CD4,HLA-DQA1,HLA-DQB1)1Ell/Tg(CD2-CD4,HLA-DQA1,HLA-DQB1)1Ell
NOD.Cg-Rag1 H2-Ab1 Tg(CD2-CD4,HLA-DQA1,HLA-DQB1)1Ell

cardiovascular system phenotype

enlarged heart
- recipient animals develop cardiomegaly by 12 weeks after transfer

heart inflammation
- recipient animals develop mononuclear cell infiltrates within heart wall by 12 weeks after transplant

myocarditis
- when young mice receive splenic lymphocytes from older NOD.DQ8/H2Ab-1 mice with heart block, myocarditis is triggered in 100% of recipients

prolonged PR interval
- 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

mammalian phenotype

cardiovascular system phenotype
- Normal - animals have normal sized hearts, normal ECG, and show no sign of autoimmune pathology

growth/size/body region phenotype

enlarged heart
- recipient animals develop cardiomegaly by 12 weeks after transfer

immune system phenotype

abnormal response to transplant
- disease onset is somewhat accelerated compared to recipients receiving total lymphocytes;
- mononuclear cells are more numerous and infiltrates more widespread than in animals that receive total splenocytes (containing CD4 T cells) in the myocardium
- 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
- when younger mice receive serum from the same older animals, no cardiac pathology is observed
- younger mice receiving splenic lymphocytes from older DQ8 transgenic, H2-Ab1-null mice with heart block develop heart block, myocarditis, and autoantibodies

heart inflammation
- recipient animals develop mononuclear cell infiltrates within heart wall by 12 weeks after transplant

increased autoantibody level
- anticardiac myosin autoantibodies reach a titer of 1:10000 in recipient mice at 12 weeks posttransfer

myocarditis
- when young mice receive splenic lymphocytes from older NOD.DQ8/H2Ab-1 mice with heart block, myocarditis is triggered in 100% of recipients

References

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):13447-52PubMed: 14570980 MGI: 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):469-77PubMed: 10078545 MGI: J:87013

Additional - H2-Ab1^tm1Gru related

Additional - Rag1^tm1Mom related

Additional - Tg(CD2-CD4,HLA-DQA1,HLA-DQB1)1Ell related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Separated PCR:Tg(CD2-CD4,HLA-DQA1,HLA-DQB1)1Ell
- Separated PCR:H2-Ab1alternate2
- Standard PCR:Rag1Alternate1
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, mice homozygous for both targeted mutations and hemizygous for the transgene may be bred together. These mice are immunodeficient and need to be maintained in a high barrier environment with sterile food and water.

Rag1-deficient, H2-Ab1-deficient mice are immunodeficient. As such, and similar to other immunodeficient strains, maintenance in high health status (specific pathogen-free) vivaria promotes overall colony health. If these animals are maintained in low health barrier rooms, the use of medicated water (e.g., sulfatrim/trimethoprim-sulfa or enrofloxacin/Baytril) is suggested to increase overall colony health.
- Additional Breeding and Husbandry Support
Appearance
- pink-eyed, albino
  Related Genotype: A/A Tyr^c/Tyr^c
Citation
When using the NOD.DQ8, H2-Ab0^null,Rag1^null mouse strain in a publication, please cite the originating article(s) and include JAX stock #006022 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Not-For-Profit & Academic Pricing

Service/Product	Description	Price
	Homozygous for Rag1<tm1Mom>, Homozygous for H2-Ab1<tm1Gru>, Carrier (Tg/?) for Tg(CD2-CD4,HLA-DQA1,HLA-DQB1)1Ell

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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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

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Also Known As:NOD.DQ8, H2-Ab0null,Rag1null

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Additional Information

Selected References

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

Allele Symbol: Tg(CD2-CD4,HLA-DQA1,HLA-DQB1)1Ell

Rag1tm1Mom

Allele Symbol: Rag1tm1Mom

H2-Ab1tm1Gru

Allele Symbol: H2-Ab1tm1Gru

Disease Terms

Research Areas By Phenotype

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

Genotype: Rag1tm1Mom related

Genotype: H2-Ab1tm1Gru related

Mammalian Phenotype Terms by Genotype

Genotype: H2-Ab1tm1Gru/H2-Ab1tm1Gru Rag1tm1Mom/Rag1tm1Mom Tg(CD2-CD4,HLA-DQA1,HLA-DQB1)1Ell/Tg(CD2-CD4,HLA-DQA1,HLA-DQB1)1EllNOD.Cg-Rag1 H2-Ab1 Tg(CD2-CD4,HLA-DQA1,HLA-DQB1)1Ell

cardiovascular system phenotype

mammalian phenotype

growth/size/body region phenotype

immune system phenotype

References

Additional - H2-Ab1tm1Gru related

Additional - Rag1tm1Mom related

Additional - Tg(CD2-CD4,HLA-DQA1,HLA-DQB1)1Ell related

Genotyping Protocols

Breeding Considerations

Appearance

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Not-For-Profit & Academic Pricing

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Also Known As:NOD.DQ8, H2-Ab0^null,Rag1^null

Rag1^tm1Mom

Allele Symbol: Rag1^tm1Mom

H2-Ab1^tm1Gru

Allele Symbol: H2-Ab1^tm1Gru

Genotype: Rag1^tm1Mom related

Genotype: H2-Ab1^tm1Gru related

Genotype: H2-Ab1^tm1Gru/H2-Ab1^tm1Gru Rag1^tm1Mom/Rag1^tm1Mom Tg(CD2-CD4,HLA-DQA1,HLA-DQB1)1Ell/Tg(CD2-CD4,HLA-DQA1,HLA-DQB1)1Ell
NOD.Cg-Rag1 H2-Ab1 Tg(CD2-CD4,HLA-DQA1,HLA-DQB1)1Ell

Additional - H2-Ab1^tm1Gru related

Additional - Rag1^tm1Mom related