These double knock-out mice exhibit absence of MHC I or MHC II cell surface expression, reduced peripheral T-cell populations, and deficiency of CD4+ and CD8+ T-cells.
Bagirath Singh, Siebens-Drake Research Institute
Genetic Background | Generation |
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|
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Targeted (Null/Knockout) | B2m | beta-2 microglobulin |
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Targeted (Null/Knockout) | Ciita | class II transactivator |
NOD.129(B6)-B2mtm1Unc C2tatm1Ccum/BhsJ is homozygous for linkage markers delineating Idd1-5, 7-10 and 13-15 loci of NOD origin and do not become diabetic. Histology indicates normal islet tissue structure with no cellular infiltration. Islets are intact and produce insulin. FACs analysis of peripheral blood cells of mice homozygote for B2mtm1Unc and C2tatm1Ccum confirmed the absence of MHC I or MHC II cell surface expression, reduced peripheral T-cell populations, deficiency of CD4+ and CD8+ T-cells and there is no difference in B-cell numbers when compared with wild-type controls. Additionally, B2mtm1Unc, C2tatm1Ccum double homozygous animals exhibit lower IgG titers and higher IgM titers than wild-type controls. Diabetic NOD females receiving purified islets from NOD.129(B6)-B2mtm1Unc C2tatm1Ccum/BhsJ transplanted under the kidney capsule remain normal glycemic for at least 147 days post transplant as compared to diabetic NOD mice with islet transplants from either NOD.129P2(B6)-B2mtm1Unc/J or NOD.129S2(B6)-C2tatm1Ccum/Flv which exhibit disease recurrence by 8 days post transplantation. Histological examination of islet grafts taken at 147 days post transplantation reveals an intact mass of insulin producing islets surrounded by cellular infiltrate. The cellular infiltrate consists mostly of CD4+ and CD8+ T-cells and macrophages. All islet grafts, independent of survival contain IFN gamma and IL10 (Young et al., 2004).
This stock is useful to help identify the mechanism by which MHC genes mediate susceptibility to T1D and the role of MHC I and II molecules in islet destruction.
Using marker assisted analysis, the NOD.129(B6)-B2mtm1Unc C2tatm1Ccum/Bhs strain is the result of intercrossing NOD.129P2(B6)-B2mtm1Unc/J to NOD.129S2(B6)-C2tatm1Ccum/Flv prior to making homozygote for both the C2tatm1Ccum and B2mtm1Unc alleles. FACS analysis of peripheral blood was used as an indicator that both the C2tatm1Ccum and B2mtm1Unc are homozygote (Young et al., 2004). In 2005, The Jackson Laboratory received NOD.129(B6)-B2mtm1Unc C2tatm1Ccum/BhsJ at generation N9F7.
Allele Name | targeted mutation 1, University of North Carolina |
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Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | b2mnull; beta2M-; beta2m0; beta2mnull; beta2mo; beta2mtm1Unc; beta2MKO; beta2-m-KO; I0; MHC-I- |
Gene Symbol and Name | B2m, beta-2 microglobulin |
Gene Synonym(s) | |
Strain of Origin | 129P2/OlaHsd |
Chromosome | 2 |
Molecular Note | Insertion of a neomycin-resistance gene into the second exon. |
Mutations Made By | Dr. Oliver Smithies, University of North Carolina at Chapel Hill |
Allele Name | targeted mutation 1, Cheong-Hee Chang |
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Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | C2tatm1Ccum; CIITA-; CIITA C-; MHC classII- |
Gene Symbol and Name | Ciita, class II transactivator |
Gene Synonym(s) | |
Strain of Origin | 129S2/SvPas |
Chromosome | 16 |
Molecular Note | A genomic fragment containing exons which encode critical regions of the protein was replaced with a neomycin selection gene. Northern blot analysis on RNA derived from homozygous mice demonstrated that no detectable protein was produced from this allele. |
Mutations Made By | Dr. Cheong-Hee Chang, Indiana University |
These mice are immunodeficient and need to be maintained in a high barrier environment with sterile food and water.
In breeding units, researchers may wish to remove the males from the pregnant females to avoid male aggression to the pups.
When using the NOD.B2mnull, C2tanull mouse strain in a publication, please cite the originating article(s) and include JAX stock #005356 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Homozygous for B2m<tm1Unc> , Homozygous forCiita<tm1Ccum> |
Frozen Mouse Embryo | NOD.129(B6)-B2m<tm1Unc> Ciita<tm1Ccum>/BhsJ Frozen Embryos | $2595.00 |
Frozen Mouse Embryo | NOD.129(B6)-B2m<tm1Unc> Ciita<tm1Ccum>/BhsJ Frozen Embryos | $2595.00 |
Frozen Mouse Embryo | NOD.129(B6)-B2m<tm1Unc> Ciita<tm1Ccum>/BhsJ Frozen Embryos | $3373.50 |
Frozen Mouse Embryo | NOD.129(B6)-B2m<tm1Unc> Ciita<tm1Ccum>/BhsJ Frozen Embryos | $3373.50 |
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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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