These NOD mice carry human CD4 and HLA-DQ6 transgenes resulting in a lack of T and B cells.
John Elliott, University of Alberta
Genetic Background | Generation |
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001976 NOD/ShiLtJ |
|
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 encoding humanized CD4 and HLA-DQ6 lack T and B cells and are free of autoimmune diabetes and cardiomyopathy, and do not develop thyroiditis.
This model is useful in adoptive transfer experiments and in studying MHC class II-based resistance and susceptibility in autoimmunity.
Congenic, H2-Ab1 deficient, NOD mice carrying transgenes encoding CD4 and a human genomic fragment containing the entire HLA-DQ6 gene (DQA1*0102, DQB1*0602, Stock No. 006023) were crossed to congenic Rag1 deficient NOD mice (Stock No. 003729), and were bred to homozygosity for the H2-Ab1tm1Gru and Rag1tm1Mom targeted mutations. The T1DR received this strain 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 N8, John F Elliott |
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Allele Type | Transgenic (Inserted expressed sequence, Humanized sequence) |
Allele Synonym(s) | DQ6 transgene; HLA-DQ6 transgene; Tg(CD4,HLA-DQA1*0102,HLADQB1*0602)1Ell |
Gene Symbol and Name | Tg(CD4,HLA-DQA1,HLA-DQB1)N8Ell, transgene insertion N8, John F Elliott |
Gene Synonym(s) | |
Promoter | HLA-DQA1, major histocompatibility complex, class II, DQ alpha 1, 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/ShiLtJ |
Chromosome | UN |
Molecular Note | The human CD4 gene lacking one exon but including its promoter was fused downstream of a mouse CD4 enhancer element then mixed with a large DNA fragment containing both HLA-DQA*0102 and HLA-DQB*0602 and injected into NOD/LtJ one celled embryos. A single founder line is maintained. |
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.DQ6, H2-Ab0null,Rag1null mouse strain in a publication, please cite the originating article(s) and include JAX stock #006024 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
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Homozygous for Rag1<tm1Mom>, Homozygous for H2-Ab1<tm1Gru>, Hemizygous (Tg/0) or Homozygous or Non carrier for Tg(CD4,HLA-DQA1,HLA-DQB1)N8Ell |
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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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