These Icosl knock-out mice exhibit severely impaired T cell dependent B cell immunological responses.
Dr. Tak Mak, University Health Network/Un of Toronto
Genetic Background | Generation |
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|
Allele Type | Gene Symbol | Gene Name |
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Targeted (Null/Knockout) | Icosl | icos ligand |
Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No gene product (protein) is detected by flow cytometry analysis of spleen cells. Homozygotes exhibit severely impaired T cell dependent B cell immunological responses, with defective B-cell isotype switching to IgG1 and IgE, and impaired T cell production of IL-4 and IL-10. Basal IgG1 serum levels are decreased in mutant mice. Following induction of allergic airway disease (AAD), an experimental model for asthma, IgE levels remain lower than wildtype levels. Antigenic challenges elicit reduced splenic germinal center size and number formation. 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 1.1kb of sequence, base pairs 153 to 507, encoding most of exon 2 and all of exon 3, including the first IgV loop ligand-binding domain 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. The donating investigator reported that the resulting male chimeric animals were crossed to female C57BL/6 mice, and then backcrossed to the same for 8 generations (see SNP note below).
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, 2 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 mixed C57BL/6J ; C57BL/6N genetic background.
Allele Name | targeted mutation 1, Tak W Mak |
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Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | B7h-; B7RP-1 KO; Icosl-; ICOSL KO |
Gene Symbol and Name | Icosl, icos ligand |
Gene Synonym(s) | |
Strain of Origin | 129P2/OlaHsd |
Chromosome | 10 |
Molecular Note | Most of exon 2 and all of exon 3 which together encode for the leader sequence, the first IgV domain and the ICOS-binding site were replaced with a neomycin-resistance gene. Loss of protein expression in mice homozygous for this deletion was established by flow cytometric analysis of spleen cells. |
Mutations Made By | Dr. Tak Mak, University Health Network/Un of Toronto |
The resulting male chimeric animals were crossed to female C57BL/6 mice, and then backcrossed to the same for 8 generations. The strain is maintained as a homozygote. SPF conditions recommended.
When using the Icosl- mouse strain in a publication, please cite the originating article(s) and include JAX stock #004657 in your Materials and Methods section.
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Service/Product | Description | Price |
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Heterozygous or Wild-type for Icosl<tm1Mak> |
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