These Cd28 knock-out mice exhibit rapid onset Type 1 diabetes in both males and females.
Dr. Jeffrey A. Bluestone, University of California, San Francisco
Genetic Background | Generation |
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|
Allele Type | Gene Symbol | Gene Name |
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Targeted (Null/Knockout) | Cd28 | CD28 antigen |
NOD mice heterozygous for the Cd28tm1Mak mutation are viable, fertile; exhibiting diabetes onset and incidence similar to NOD. NOD mice homozygous for Cd28tm1Mak experience rapid onset Type 1 diabetes in both males and females. When stimulated with anti-Cd3 mAB, T cells from CD28 deficient NOD mice proliferate poorly when compared with wildtype controls. Nor do T cells proliferate in culture after the mice have been immunized with ovalbumin (OVA) in complete Freunds adjuvant. The IL-2 level of T-cells from mice that have been stimulated with either anti-Cd3 or OVA was significantly reduced. However, when challenged with GAD the CD28 deficient mice produced normal levels of IL-2. RT-PCR indicates a dramatic increase in the amount of IFNgamma and decreased IL4 compared to heterozygous controls. 1.5% of CD4 T cells from homozygous mice express CD25, while 6.5% of the CD4 T cells express CD25 in their wildtype cohorts.
This model is useful for studying the CTLA4/CD28:CD80/CD86 pathways in the regulation of self tolerance and susceptibility to autoimmune diseases.
Cd28, located on Chr. 1, 30.1cM, is involved in costimulatory signaling important for T cell activation.
A construct containing a neomycin expression cassette replacing part of exon 2 of Cd28 was transfected into D3 (129S2/SvPas derived) embryonic stem cells (ES cells). These ES cells were injected into C57BL/6 blastocysts. As reported by Lenschow et al 1996, chimeric founders were initially mated to C57BL/6 and intercrossed to generate Cd28 deficient mice. B6 congenic mice homozygous for the mutation were subsequently mated to NOD for 4 generations, Lenschow et al 1996, prior to making homozygous. In 2006, the T1DR received mice heterozygous for the mutation at generation N11.
Allele Name | targeted mutation 1, Tak Mak |
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Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | CD28-; CD28KO |
Gene Symbol and Name | Cd28, CD28 antigen |
Gene Synonym(s) | |
Strain of Origin | 129S2/SvPas |
Chromosome | 1 |
Molecular Note | A genomic fragment containing part of exon 2 was replaced by a neomycin resistance cassette. Flow-cytometry analysis on peripheral blood lymphocytes demonstrated that the protein was not expressed in these cells in homozygous mice. |
Mutations Made By | Dr. Tak Mak, University Health Network/Un of Toronto |
When maintaining a live colony, heterozygous mice may be bred together.
When using the CD28- mouse strain in a publication, please cite the originating article(s) and include JAX stock #004761 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous or Wild-type for Cd28<tm1Mak> |
Frozen Mouse Embryo | NOD.129S2(B6)-Cd28<tm1Mak>/JbsJ Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | NOD.129S2(B6)-Cd28<tm1Mak>/JbsJ Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | NOD.129S2(B6)-Cd28<tm1Mak>/JbsJ Frozen Embryo | $3373.50 |
Frozen Mouse Embryo | NOD.129S2(B6)-Cd28<tm1Mak>/JbsJ Frozen Embryo | $3373.50 |
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