Homozygotes exhibit severely impaired T cell dependent B cell immunological responses and defective isotype switching. The number and size of splenic germinal centers from antigen challenged mutant mice is reduced, and basal IgG1 serum level of 8 week-old homozygous mutant mice is reduced. This mutant mouse strain may be useful in studies of T cell dependent B cell immunological responses and T cell activation.
Dr. Tak Mak, University Health Network/Un of Toronto
Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. In wildtype mice, ICOS protein is expressed on activated but not resting T cells, and shows T-cell co-stimulatory function. It delivers a co-stimulatory signal that is essential both for efficient interaction between T and B cells and for normal antibody responses to T-cell-dependent antigens. In homozygous targeted mutation mice, gene product (protein) is undetected on activated T cells by flow cytometry analysis. Homozygotes exhibit severely impaired T cell dependent B cell immunological responses and defective isotype switching. Histological analysis reveals a reduction in the number and size of splenic germinal centers from antigen challenged mutant mice. The basal IgG1 serum level of 8 week-old homozygous mutant mice is 30% of the level found in the wildtype. This mutant mouse strain may be useful in studies of T cell dependent B cell immunological responses and T cell activation.
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt 2.8kb of sequence encoding most of exon 2 and all of exons 3 and 4 of the targeted gene. The construct was electroporated into 129P2/OlaHsd derived E14 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts
A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, 3 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a C57BL/6N genetic background.
|Allele Name||targeted mutation 1, Tak Mak|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||targeted mutation 1, Tak Mak; Icostm1Mak|
|Gene Symbol and Name||Icos, inducible T cell co-stimulator|
|Gene Synonym(s)||AILIM; CD278; CVID1; Ailim|
|Strain of Origin||129P2/OlaHsd|
|Molecular Note||Most of exon 2 and all of exons 3 and 4 were replaced by a neomycin selection cassette inserted by homologous recombination. The deleted region encoded the putative Icosl binding site, the transmembrane domain, and a portion of the intracellular domain including the YMFM motif that potentially binds lipid phosphotidylinositol 3 kinase. Flow cytometric analysis indicated an absence of protein on the surface of activated T cells obtained from homozygous mutant mice.|
|Mutations Made By|| |
Dr. Tak Mak, University Health Network/Un of Toronto
The resulting male chimeric animals were crossed to C57BL/6 female mice, and then backcrossed to the same for 10 generations. The strain is maintained as a homozygote.
When using the ICOS KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #004859 in your Materials and Methods section.
|Heterozygous for Icos<tm1Mak>|
We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.
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