Description

Strain Information

Former Names B6.129P2-Icoslgtm1Mak/J    (Changed: 06-MAY-05 ) B6.129P2-Icosltm1Mak/J    (Changed: 17-FEB-05 ) B6.129P2-Icosltm1Mak    (Changed: 15-DEC-04 ) Type Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Mating System Homozygote x Homozygote         (Female x Male) Species laboratory mouse Generation N8F?+F10 (27-APR-08)   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. 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.

Control Information

	Control
	000664 C57BL/6J	(approximate)
Considerations for Choosing Controls

Additional Web Information

Congenic Nomenclature
Genetic Quality Control Annual Report

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.

Icosl^tm1Mak/Icosl^tm1Mak

        involves: 129P2/OlaHsd * C57BL/6

• hematopoietic system phenotype
• abnormal T-helper 2 cell differentiation (MGI Ref ID J:84668)
  • impaired TH2 differentiation
• abnormal class switch recombination (MGI Ref ID J:84668)
  • B cell isotype switching was impaired
• abnormal spleen morphology (MGI Ref ID J:84668)
• decreased spleen germinal center number (MGI Ref ID J:84668)
  • the mean number of germinal centers is severely reduced
• decreased spleen germinal center size (MGI Ref ID J:84668)
  • the size of the germinal centers is severely reduced
• immune system phenotype
• *normal* immune system phenotype (MGI Ref ID J:84668)
  • T and B cell development was unaffected and the overall composition of T and B cells in the spleen was normal
• abnormal T-helper 2 cell differentiation (MGI Ref ID J:84668)
  • impaired TH2 differentiation
• abnormal immune system physiology (MGI Ref ID J:84668)
  • affinity maturation of IgG1 was impaired
  • IgE response was reduced to sensitization with aerosolized antigen after repeated immunization
  • interaction between T and B cells was impaired
• abnormal class switch recombination (MGI Ref ID J:84668)
  • B cell isotype switching was impaired
• decreased IgG1 level (MGI Ref ID J:84668)
  • IgG1 is the only immunoglobulin to be significantly reduced in amount
• decreased inflammatory response (MGI Ref ID J:84668)
  • inflammatory response was significantly reduced
  • fewer T cells producing IL4 and IL-10
  • IFN-gamma production unaffected
• abnormal spleen morphology (MGI Ref ID J:84668)
• decreased spleen germinal center number (MGI Ref ID J:84668)
  • the mean number of germinal centers is severely reduced
• decreased spleen germinal center size (MGI Ref ID J:84668)
  • 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:

Icosl^tm1Mak related

Immunology and Inflammation Research
Immunodeficiency (B and T cell deficiency)
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		Icosltm1Mak
Allele Name		targeted mutation 1, Tak W Mak
Allele Type		Targeted (knock-out)
Common Name(s)		B7RP-1 KO; Icosl-;
Mutation Made By		Tak Mak,   University Health Network/Un of Toronto
Strain of Origin		129P2/OlaHsd
ES Cell Line Name		E14.1
ES Cell Line Strain		129P2/OlaHsd
Gene Symbol and Name		Icosl, icos ligand
Chromosome		10
Gene Common Name(s)		AU044799; B7-H2; B7H2; B7RP-1; B7RP1; B7h; BG071784; CD275; EST BG071784; GL50; GL50-B; ICOS-L; KIAA0653; LICOS; RGD1562791; expressed sequence AU044799;
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 establishedby flow cytometric analysis of spleen cells. [MGI Ref ID J:84668]

Genotyping

Genotyping Information

Genotyping Protocols

Icosl^tm1Mak, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

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):765-72. [PubMed: 12833154]  [MGI Ref ID J:84668]

Additional References

Icosl^tm1Mak related

Akbari O; Stock P; Meyer EH; Freeman GJ; Sharpe AH; Umetsu DT; DeKruyff RH. 2008. ICOS/ICOSL interaction is required for CD4+ invariant NKT cell function and homeostatic survival. J Immunol 180(8):5448-56. [PubMed: 18390727]  [MGI Ref ID J:134254]

Gajewska BU; Tafuri A; Swirski FK; Walker T; Johnson JR; Shea T; Shahinian A; Goncharova S; Mak TW; Stampfli MR; Jordana M. 2005. B7RP-1 is not required for the generation of Th2 responses in a model of allergic airway inflammation but is essential for the induction of inhalation tolerance. J Immunol 174(5):3000-5. [PubMed: 15728513]  [MGI Ref ID J:97721]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX12

Colony Maintenance

Breeding & Husbandry	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.
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	(approximate)
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

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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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Terms of Use

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