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- Description
- Disease & phenotype
- Genes & alleles
- Genotyping
- Health & care
- References
- Pricing & purchasing
- Terms of use
Description
The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.
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 and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation ?+N1p (07-NOV-04)
Generation DefinitionsDonating Investigator Dr. 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. 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 Information
| Control | ||
|---|---|---|
| 000664 C57BL/6J | (approximate) | |
| Considerations for Choosing Controls | ||
Phenotype
Phenotype Information
View Mammalian Phenotype Terms
Mammalian Phenotype Terms provided by MGI
assigned by genotype
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Icosltm1Mak/Icosltm1Mak
involves: 129P2/OlaHsd * C57BL/6
- hematopoietic system phenotype
- abnormal T-helper 2 cell differentiation
- impaired TH2 differentiation (MGI Ref ID J:84668)
- abnormal class switch recombination
- B cell isotype switching was impaired (MGI Ref ID J:84668)
- abnormal spleen morphology (MGI Ref ID J:84668)
- immune system phenotype
- *normal* immune system phenotype
- T and B cell development was unaffected and the overall composition of T and B cells in the spleen was normal (MGI Ref ID J:84668)
- abnormal T-helper 2 cell differentiation
- impaired TH2 differentiation (MGI Ref ID J:84668)
- abnormal immune system physiology
- abnormal spleen morphology (MGI Ref ID J:84668)
- cellular phenotype
- abnormal T-helper 2 cell differentiation
- impaired TH2 differentiation (MGI Ref ID J:84668)
- abnormal class switch recombination
- B cell isotype switching was impaired (MGI Ref ID J:84668)
This mouse can be used to support research in many areas including:Icosltm1Mak related
Immunology, Inflammation and Autoimmunity 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 provided by MGI
| Allele Symbol | Icosltm1Mak | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, Tak W Mak | ||
| Allele Type | Targeted (knock-out) | ||
| Common Name(s) | B7RP-1 KO; ICOSL KO; Icosl-; | ||
| Mutation Made By | Dr. 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; 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
Icosltm1Mak, Standard PCR
Helpful Links
Genotyping resources and troubleshooting
References
References provided by MGI
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
Icosltm1Mak relatedAkbari 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]
Choi YS; Kageyama R; Eto D; Escobar TC; Johnston RJ; Monticelli L; Lao C; Crotty S. 2011. ICOS Receptor Instructs T Follicular Helper Cell versus Effector Cell Differentiation via Induction of the Transcriptional Repressor Bcl6. Immunity 34(6):932-46. [PubMed: 21636296] [MGI Ref ID J:174012]
Clay BS; Shilling RA; Bandukwala HS; Moore TV; Cannon JL; Welcher AA; Weinstock JV; Sperling AI. 2009. Inducible costimulator expression regulates the magnitude of Th2-mediated airway inflammation by regulating the number of Th2 cells. PLoS One 4(11):e7525. [PubMed: 19888475] [MGI Ref ID J:155428]
Fu T; He Q; Sharma P. 2011. The ICOS/ICOSL Pathway Is Required for Optimal Antitumor Responses Mediated by Anti-CTLA-4 Therapy. Cancer Res 71(16):5445-54. [PubMed: 21708958] [MGI Ref ID J:175451]
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]
Kadkhoda K; Wang S; Fan Y; Qiu H; Basu S; Halayko AJ; Yang X. 2011. ICOS ligand expression is essential for allergic airway hyperresponsiveness. Int Immunol 23(4):239-49. [PubMed: 21402623] [MGI Ref ID J:172077]
Kadkhoda K; Wang S; Joyee AG; Fan Y; Yang J; Yang X. 2010. Th1 cytokine responses fail to effectively control Chlamydia lung infection in ICOS ligand knockout mice. J Immunol 184(7):3780-8. [PubMed: 20190137] [MGI Ref ID J:160088]
Maeda S; Fujimoto M; Matsushita T; Hamaguchi Y; Takehara K; Hasegawa M. 2011. Inducible Costimulator (ICOS) and ICOS Ligand Signaling Has Pivotal Roles in Skin Wound Healing via Cytokine Production. Am J Pathol 179(5):2360-9. [PubMed: 21925472] [MGI Ref ID J:177367]
Maynard CL; Hatton RD; Helms WS; Oliver JR; Stephensen CB; Weaver CT. 2009. Contrasting roles for all-trans retinoic acid in TGF-beta-mediated induction of Foxp3 and Il10 genes in developing regulatory T cells. J Exp Med 206(2):343-57. [PubMed: 19204112] [MGI Ref ID J:146450]
Moore TV; Clay BS; Cannon JL; Histed A; Shilling RA; Sperling AI. 2011. Inducible costimulator controls migration of T cells to the lungs via down-regulation of CCR7 and CD62L. Am J Respir Cell Mol Biol 45(4):843-50. [PubMed: 21421907] [MGI Ref ID J:190213]
Nie X; Cai G; Zhang W; Wang H; Wu B; Li Q; Shen Q. 2012. Lipopolysaccharide mediated mast cells induce IL-10 producing regulatory T Cells through the ICOSL/ICOS axis. Clin Immunol 142(3):269-79. [PubMed: 22154192] [MGI Ref ID J:181372]
Pepper M; Pagan AJ; Igyarto BZ; Taylor JJ; Jenkins MK. 2011. Opposing signals from the bcl6 transcription factor and the interleukin-2 receptor generate T helper 1 central and effector memory cells. Immunity 35(4):583-95. [PubMed: 22018468] [MGI Ref ID J:177635]
Prevot N; Briet C; Lassmann H; Tardivel I; Roy E; Morin J; Mak TW; Tafuri A; Boitard C. 2010. Abrogation of ICOS/ICOS ligand costimulation in NOD mice results in autoimmune deviation toward the neuromuscular system. Eur J Immunol 40(8):2267-76. [PubMed: 20544729] [MGI Ref ID J:165756]
Health & husbandry
The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.
Health & Colony Maintenance Information
Animal Health Reports
Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.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. Diet Information LabDiet® 5K52/5K67
Pricing and Purchasing
Pricing, Supply Level & Notes, Controls
| Pricing for USA, Canada and Mexico shipping destinations |
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Cryopreserved
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $2250.00 At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Supply Notes
- Cryorecovery - Standard.
Progeny testing is not required.
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory 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.Cryorecovery to establish a Dedicated Supply for greater quantities of mice.
Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).
| Pricing for International shipping destinations |
|
Cryopreserved
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $2925.00 At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Supply Notes
- Cryorecovery - Standard.
Progeny testing is not required.
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory 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.Cryorecovery to establish a Dedicated Supply for greater quantities of mice.
Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).
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Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
General Supply Notes
- Genomic DNA is available for this strain from the Mouse DNA Resource.
Control Information
| Control | ||
|---|---|---|
| 000664 C57BL/6J | (approximate) | |
| Considerations for Choosing Controls | ||
| Control Pricing Information for Genetically Engineered Mutant Strains. | ||
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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.Ordering Information
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