These NOD mice carry human CD4 and HLA- DQ8 transgenes along with the Rag1tm1Mom and Ab1tm1Gru targeted mutations and are free from both autoimmune diabetes and cardiomyopathy.
John Elliott, University of Alberta
Genetic Background | Generation |
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|
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 |
Allele Type |
---|
Transgenic (Inserted expressed sequence, Humanized sequence) |
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.
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.
Expressed Gene | HLA-DQA1, major histocompatibility complex, class II, DQ alpha 1, human |
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Expressed Gene | CD4, CD4 molecule, human |
Expressed Gene | HLA-DQB1, major histocompatibility complex, class II, DQ beta 1, human |
Site of Expression |
Allele Name | targeted mutation 1, Peter Mombaerts |
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Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | Rag-; Rag1tm1Mom; RAG-1-; Rag1-; RAG1null; 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 |
Allele Name | targeted mutation 1, Michael J Grusby |
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Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | [KO]Abb; Abbeta-; Ab1tm1Gru; Abb-; Abbtm1; Abeta-; Abetab-; C2-; H2-Ab1-; H2-Ab1tm1Glm; I-Ab-; IAb-; IAbeta-; I-Abetab-; 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 |
Allele Name | transgene insertion 1, John F Elliott |
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Allele Type | Transgenic (Inserted expressed sequence, Humanized sequence) |
Allele Synonym(s) | DQ8+; human CD4, DQ8 transgene; human CD4, DQA1*0301, DQB1*0302 transgene; Tg(CD2-CD4,HLA-DQA1*0301,HLA-DQB1*0302)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-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. |
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.
When using the NOD.DQ8, H2-Ab0null,Rag1null mouse strain in a publication, please cite the originating article(s) and include JAX stock #006022 in your Materials and Methods section.
Facility Barrier Level Descriptions
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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