These mice carry a targeted deletion of 3 exons in the Icos (inducible T cell co-stimulator) gene. T cell activation and proliferation are defective in the absence of expression. Homozygous knockout mice show a greatly enhanced susceptibility to experimental autoimmune encephalomyelitis, indicating that the gene has a protective role in inflammatory autoimmune diseases. On the NOD background, the presence of protein is indispensable for the development of insulitis and hyperglycemia in NOD mice. This strain is useful in studies of the induction of the autoimmune process that leads to diabetes.
Dr. Richard A. Flavell, Yale University School of MedicineRead More +
Mice that are homozygous for the targeted deletion are viable and fertile. T cell activation and proliferation are defective in the absence of expression. In addition, T cells from homozygotes fail to produce interleukin-4 when differentiated in vitro or when primed in vivo. ICOS is required for humoral immune responses after immunization with several antigens. Homozygous knockout mice show a greatly enhanced susceptibility to experimental autoimmune encephalomyelitis, indicating that the gene has a protective role in inflammatory autoimmune diseases. On the NOD background, the presence of protein is indispensable for the development of insulitis and hyperglycemia in NOD mice. In T cells, the deletion of the gene results in a decreased production of the Th1 cytokine IFN-gamma, whereas the numbers of regulatory T cells remained unchanged. This strain is useful in studies of the induction of the autoimmune process that leads to diabetes.
A targeting construct, replacing three exons (encoding all of the amino-acid sequences except the leader peptide) with a neomycin resistance gene driven by the PGK promoter, was transfected into 129S1/Sv Oca2+ Tyr+ Kitl+-derived W9.5 embryonic stem (ES) cells. This line was crossed with C57BL/6 perhaps 1 or 2 generations before being backcrossed to NOD for 10 generations by the donating laboratory.
|Allele Name||targeted mutation 1, Richard A Flavell|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Icos, inducible T cell co-stimulator|
|Gene Synonym(s)||AILIM; Ailim; CD278; CVID1|
|Strain of Origin||129S1/Sv-Oca2<+> Tyr<+> Kitl<+>|
|Molecular Note||The three exons for all of the amino acid coding sequence except the leader peptide were replaced with a PGK-neomycin resistance cassette. Absence of protein product was demonstrated immunologically.|
|Mutations Made By|| |
Dr. Richard Flavell, Yale University School of Medicine
|Please inquire about possible genotypes.|
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided,
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