Overview

Also Known As:Icosl-

These Icosl knock-out mice exhibit severely impaired T cell dependent B cell immunological responses.

Donating Investigator

Dr. Tak Mak, University Health Network / University of Toronto

Genetic overview

Genetic Background	Generation

Icosl^tm1Mak

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Icosl	icos ligand

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Research Applications

Immunology, Inflammation and Autoimmunity Research
Internal/Organ Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

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.

Development

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.

Control Suggestions

Approximate Controls

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Mak TW; Shahinian A; Yoshinaga SK; Wakeham A; Boucher LM; Pintilie M; Duncan G; Gajewska BU; Gronski M; Eriksson U; Odermatt B; Ho A; Bouchard D; Whorisky JS; Jordana M; Ohashi PS; Pawson T; Bladt F; Tafuri A. 2003. Costimulation through the inducible costimulator ligand is essential for both T helper and B cell functions in T cell-dependent B cell responses. Nat Immunol 4(8):765-72PubMed: 12833154 MGI: J:84668

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Genetics

Icosl^tm1Mak

Allele Symbol: Icosl^tm1Mak

Allele Name	targeted mutation 1, Tak W Mak
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 / University of Toronto

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Genotype: Icosl^tm1Mak related

Immunology, Inflammation and Autoimmunity Research
- Lymphoid Tissue Defects
  - B and T cell deficiency
- Immunodeficiency
  - B and T cell deficiency
Internal/Organ Research
- Lymphoid Tissue Defects
  - B and T cell deficiency

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Icosl^tm1Mak/Icosl^tm1Mak
involves: 129P2/OlaHsd * C57BL/6

mammalian phenotype

immune system phenotype
- Normal - T and B cell development was unaffected and the overall composition of T and B cells in the spleen was normal

hematopoietic system phenotype

abnormal spleen morphology

abnormal T-helper 2 cell differentiation
- impaired TH2 differentiation

decreased IgG1 level
- IgG1 is the only immunoglobulin to be significantly reduced in amount

decreased spleen germinal center size
- the size of the germinal centers is severely reduced

abnormal class switch recombination
- B cell isotype switching was impaired

decreased spleen germinal center number
- the mean number of germinal centers is severely reduced

immune system phenotype

abnormal immune system physiology
- IgE response was reduced to sensitization with aerosolized antigen after repeated immunization
- affinity maturation of IgG1 was impaired
- interaction between T and B cells was impaired

decreased IgG1 level
- IgG1 is the only immunoglobulin to be significantly reduced in amount

decreased inflammatory response
- IFN-gamma production unaffected
- inflammatory response was significantly reduced
- fewer T cells producing IL4 and IL-10

decreased spleen germinal center size
- the size of the germinal centers is severely reduced

decreased spleen germinal center number
- the mean number of germinal centers is severely reduced

abnormal spleen morphology

abnormal class switch recombination
- B cell isotype switching was impaired

abnormal T-helper 2 cell differentiation
- impaired TH2 differentiation

References

Mak TW; Shahinian A; Yoshinaga SK; Wakeham A; Boucher LM; Pintilie M; Duncan G; Gajewska BU; Gronski M; Eriksson U; Odermatt B; Ho A; Bouchard D; Whorisky JS; Jordana M; Ohashi PS; Pawson T; Bladt F; Tafuri A. 2003. Costimulation through the inducible costimulator ligand is essential for both T helper and B cell functions in T cell-dependent B cell responses. Nat Immunol 4(8):765-72PubMed: 12833154 MGI: J:84668

Additional - Icosl^tm1Mak related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Icosl
- Genotyping resources and troubleshooting
Breeding Considerations

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.
- Additional Breeding and Husbandry Support
Citation
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.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
> >	Heterozygous or Wild-type for Icosl<tm1Mak>

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

The Jackson Laboratory's Genotype Promise

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.

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Additional Use Restrictions Apply

Use of MICE by companies or for-profit entities requires a license prior to shipping.

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Also Known As:Icosl-

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Selected References

Icosltm1Mak

Allele Symbol: Icosltm1Mak

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Genotype: Icosltm1Mak related

Mammalian Phenotype Terms by Genotype

Genotype: Icosltm1Mak/Icosltm1Makinvolves: 129P2/OlaHsd * C57BL/6

mammalian phenotype

hematopoietic system phenotype

immune system phenotype

References

Additional - Icosltm1Mak related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

Icosl^tm1Mak

Allele Symbol: Icosl^tm1Mak

Genotype: Icosl^tm1Mak related

Genotype: Icosl^tm1Mak/Icosl^tm1Mak
involves: 129P2/OlaHsd * C57BL/6

Additional - Icosl^tm1Mak related