Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Mating System Homozygote x Homozygote         (Female x Male) Species laboratory mouse Generation N10F?+7 (06-DEC-07)   Donating Investigator Tak Mak,   University Health Network/Un of Toronto

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. 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.

Development
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

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Icos

007019

B6.129S1-Icostm1Flv/J

View Strains carrying other alleles of Icos     (1 strain)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Icos^tm1Mak/Icos^tm1Mak

        involves: 129P2/OlaHsd * C57BL/6

• hematopoietic system phenotype
• abnormal class switch recombination (MGI Ref ID J:66702)
  • B cell isotype switching was impaired in both primary and secondary T-cell dependent B cell response
• abnormal spleen morphology (MGI Ref ID J:66702)
• decreased spleen germinal center number (MGI Ref ID J:66702)
  • the mean number of germinal centers is severely reduced
• decreased spleen germinal center size (MGI Ref ID J:66702)
  • the size of the germinal centers is severely reduced
• decreased T cell proliferation (MGI Ref ID J:66702)
  • impaired early stage T-cell proliferation to some stimuli
  • however, T cell development was unaffected
• immune system phenotype
• abnormal immune system physiology (MGI Ref ID J:66702)
  • interactions between T and B cells were impaired
• abnormal B cell physiology (MGI Ref ID J:66702)
  • B cell proliferation normal
  • no impairment in T-cell independent response and B cell development was normal
• abnormal class switch recombination (MGI Ref ID J:66702)
  • B cell isotype switching was impaired in both primary and secondary T-cell dependent B cell response
• decreased IgE level (MGI Ref ID J:66702)
  • after stimulation with T-cell dependent antigen
• decreased IgG1 level (MGI Ref ID J:66702)
  • IgG1 only immunoglobulin significantly reduced in amount
• abnormal T cell physiology (MGI Ref ID J:66702)
  • fewer T cells producing IL4
  • IFN-gamma production unaffected
• decreased T cell proliferation (MGI Ref ID J:66702)
  • impaired early stage T-cell proliferation to some stimuli
  • however, T cell development was unaffected
• abnormal spleen morphology (MGI Ref ID J:66702)
• decreased spleen germinal center number (MGI Ref ID J:66702)
  • the mean number of germinal centers is severely reduced
• decreased spleen germinal center size (MGI Ref ID J:66702)
  • the size of the germinal centers is severely reduced

View Research Applications

Research Applications

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

Icos^tm1Mak related

Immunology and Inflammation Research
Lymphoid Tissue Defects (B and T cell deficiency)

Internal/Organ Research
Lymphoid Tissue Defects (B and T cell deficiency)

Genes & Alleles

Gene & Allele Information

Allele Symbol		Icostm1Mak
Allele Name		targeted mutation 1, Tak Mak
Allele Type		Targeted (knock-out)
Common Name(s)		ICOS-;
Mutation Made By		Tak Mak,   University Health Network/Un of Toronto
Strain of Origin		129P2/OlaHsd
ES Cell Line Name		E14
ES Cell Line Strain		129P2/OlaHsd
Gene Symbol and Name		Icos, inducible T-cell co-stimulator
Chromosome		1
Gene Common Name(s)		AILIM; CD278; MGC39850;
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. [MGI Ref ID J:66702]

Genotyping

Genotyping Information

Genotyping Protocols

Icos^tm1Mak, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Tafuri A; Shahinian A; Bladt F; Yoshinaga SK; Jordana M; Wakeham A; Boucher LM; Bouchard D; Chan VS; Duncan G; Odermatt B; Ho A; Itie A; Horan T; Whoriskey JS; Pawson T; Penninger JM; Ohashi PS; Mak TW. 2001. ICOS is essential for effective T-helper-cell responses. Nature 409(6816):105-9. [PubMed: 11343123]  [MGI Ref ID J:66702]

Additional References

Icos^tm1Mak related

Bergqvist P; Gardby E; Stensson A; Bemark M; Lycke NY. 2006. Gut IgA class switch recombination in the absence of CD40 does not occur in the lamina propria and is independent of germinal centers. J Immunol 177(11):7772-83. [PubMed: 17114448]  [MGI Ref ID J:140700]

Bertram EM; Tafuri A; Shahinian A; Chan VS; Hunziker L; Recher M; Ohashi PS; Mak TW; Watts TH. 2002. Role of ICOS versus CD28 in antiviral immunity. Eur J Immunol 32(12):3376-85. [PubMed: 12432568]  [MGI Ref ID J:80851]

Bossaller L; Burger J; Draeger R; Grimbacher B; Knoth R; Plebani A; Durandy A; Baumann U; Schlesier M; Welcher AA; Peter HH; Warnatz K. 2006. ICOS deficiency is associated with a severe reduction of CXCR5+CD4 germinal center Th cells. J Immunol 177(7):4927-32. [PubMed: 16982935]  [MGI Ref ID J:139302]

Guo F; Iclozan C; Suh WK; Anasetti C; Yu XZ. 2008. CD28 controls differentiation of regulatory T cells from naive CD4 T cells. J Immunol 181(4):2285-91. [PubMed: 18684917]  [MGI Ref ID J:140198]

Marks E; Verolin M; Stensson A; Lycke N. 2007. Differential CD28 and Inducible Costimulatory Molecule Signaling Requirements for Protective CD4+ T-Cell-Mediated Immunity against Genital Tract Chlamydia trachomatis Infection. Infect Immun 75(9):4638-47. [PubMed: 17635872]  [MGI Ref ID J:123920]

Suh WK; Tafuri A; Berg-Brown NN; Shahinian A; Plyte S; Duncan GS; Okada H; Wakeham A; Odermatt B; Ohashi PS; Mak TW. 2004. The inducible costimulator plays the major costimulatory role in humoral immune responses in the absence of CD28. J Immunol 172(10):5917-23. [PubMed: 15128772]  [MGI Ref ID J:89869]

Vidric M; Bladt AT; Dianzani U; Watts TH. 2006. Role for inducible costimulator in control of Salmonella enterica serovar Typhimurium infection in mice. Infect Immun 74(2):1050-61. [PubMed: 16428752]  [MGI Ref ID J:105003]

Vidric M; Suh WK; Dianzani U; Mak TW; Watts TH. 2005. Cooperation between 4-1BB and ICOS in the immune response to influenza virus revealed by studies of CD28/ICOS-deficient mice. J Immunol 175(11):7288-96. [PubMed: 16301634]  [MGI Ref ID J:122143]

Vu F; Dianzani U; Ware CF; Mak T; Gommerman JL. 2008. ICOS, CD40, and lymphotoxin beta receptors signal sequentially and interdependently to initiate a germinal center reaction. J Immunol 180(4):2284-93. [PubMed: 18250437]  [MGI Ref ID J:131998]

Wilson EH; Zaph C; Mohrs M; Welcher A; Siu J; Artis D; Hunter CA. 2006. B7RP-1-ICOS interactions are required for optimal infection-induced expansion of CD4+ Th1 and Th2 responses. J Immunol 177(4):2365-72. [PubMed: 16887998]  [MGI Ref ID J:138389]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX12

Colony Maintenance

Breeding & Husbandry	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.
Mating System	Homozygote x Homozygote         (Female x Male)
Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement.

Supply Notes

Usually shipped between four and eight weeks of age. This strain is included in the Induced Mutant Resource Colony collection. Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

General Terms and Conditions

See Terms of Use

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.

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Ordering and Purchasing Information

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Contact Information
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Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

For Licensing and Use Restrictions view the link(s) below:
- Strain(s) not available to companies or for-profit entities.

Contact information

General inquiries

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phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of MICE, products or services, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.

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The foregoing represents the General Terms and Conditions applicable to The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, products and services by The Jackson Laboratory, and by its licensees and distributors.

Acceptance of delivery of MICE, products or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on The Jackson Laboratory, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, products services by The Jackson Laboratory.