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Former Names NOD.Cg-Tnfsf4tm1Shr/DoiJ (Changed: 17-DEC-04 ) Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Background Strain NOD Donor Strain 129S4 from J1 ES cell line H2 Haplotype g7 Generation N8F4+F5p (09-NOV-05)
Generation DefinitionsDonating Investigator Christophe Benoist, Joslin Diabetes Center Appearance
pink-eyed albino
Related Genotype: A/? Tyrc/TyrcDescription
Tnfsf4tm1Shrhomozygous mice are viable, fertile, normal in size, and do not display any gross physical or behavioral abnormalities. There is no detectable expression of Tnfsf4 on activated dendritic cells, T-cells and B-cells derived from spleen or lymph nodes by FAC analysis or ELISA. Additionally, the number of B-cells, T-cells, T-cell subsets and expression of CD25 and CD69 in spleen and lymph nodes are comparable to NOD controls. All Tnfsf4 homozygous mice are completely protected from diabetes and histological evaluation seldom shows insulitis when compared to wild-type controls, which exhibit a normal NOD like diabetes incidence and onset.This model is useful for studying co-stimulation, dendritic cell function and the role of Tnfsf4 on CD4 positive T cell responses in Type 1 Diabetes.
Development
A construct containing a neomycin expression cassette replaced the entire extracellular domain and part of the 3' untranslated region of Tnfsf4 (commonly referred to as Ox40l and cloned from 129/Sv mouse genomic library) was transfected into J1 embryonic stem cells (ES cells). These ES cells were injected into C57BL/6 blastocysts. To establish a colony with germ line transmission, chimeric mice were backcrossed to 129/Sv (Chen et, al, 1999). Martin-Orozco et al. 2003, subsequently backcrossed this mutation to NOD/Lt. A genome wide scan confirmed that markers for Idd1, Idd3, Idd5 and Idd10 were homozygous for the NOD allele. In 2004, the Type 1 Diabetes Resource received NOD.129(B6)-Tnfsf4tm1Shr/DoiJ at generation N8F4.
| Control | ||
|---|---|---|
| 001976 NOD/ShiLtJ | ||
| Considerations for Choosing Controls | ||
Strains carrying other alleles of Tnfsf4
002671 B6.PERA-Tnfsf4Ath1-PERA/EiJ/Pgn 005969 B6Cr.129S4-Tnfsf4tm1Sug/Pgn 005967 C57BL/6J-Tg(Mt1-Tnfsf4)1Pgn/Pgn 005968 C57BL/6J-Tg(Mt1-Tnfsf4)2Pgn/Pgn View Strains carrying other alleles of Tnfsf4 (4 strains)
View Related Disease (OMIM) Terms
Related Disease (OMIM) Terms provided by MGI
- Model with phenotypic similarity to human disease where etiologies are distinct. Human genes are associated with this disease. Orthologs of these genes do not appear in the mouse genotype(s).
Diabetes Mellitus, Insulin-Dependent; IDDM
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Myocardial Infarction, Susceptibility to (TNFSF4)
View Mammalian Phenotype Terms
Mammalian Phenotype Terms provided by MGI
assigned by genotype
Tnfsf4tm1Shr/Tnfsf4tm1Shr
NOD.129S4-Tnfsf4tm1Shr
- immune system phenotype
- decreased susceptibility to autoimmune diabetes
- NOD mice homozygous for Tnfsf4tm1Shr and homozygous at the NOD alleles Idd1, Idd3, Idd5 and Idd10 are completely protected from diabetes during 30 weeks of observation while wild-type NOD controls show the expected course and penetrance of diabetes (MGI Ref ID J:86926)
View Research Applications
Research Applications
This mouse can be used to support research in many areas including:
Diabetes and Obesity Research
Type 1 Diabetes (IDDM)
resistant
Immunology, Inflammation and Autoimmunity Research
Autoimmunity
Type 1 Diabetes
| Allele Symbol | Tnfsf4tm1Shr | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, Arlene H Sharpe | ||
| Allele Type | Targeted (knock-out) | ||
| Common Name(s) | OX40Lo; Ox40L-/-; | ||
| Mutation Made By | Arlene Sharpe, Harvard Medical School | ||
| Strain of Origin | 129S4/SvJae | ||
| ES Cell Line Name | J1 | ||
| ES Cell Line Strain | 129S4/SvJae | ||
| Gene Symbol and Name | Tnfsf4, tumor necrosis factor (ligand) superfamily, member 4 | ||
| Chromosome | 1 | ||
| Gene Common Name(s) | Ath-1; Ath1; CD134L; CD252; GP34; OX-40L; OX40L; OX4OL; Ox40 ligand; Ox40l; TXGP1; Txgp1l; atherosclerosis 1; tax-transcriptionally activated glycoprotein 1 ligand; | ||
| Molecular Note | A neomycin selection cassette inserted by homologous recombination replaced the exon encoding the entire extracellular domain and a portion of the 3' untranslated region. Protein was undetected by flow cytometric analysis of activated homozygous mutant dendritic cells. [MGI Ref ID J:59203] | ||
Martin-Orozco N; Chen Z; Poirot L; Hyatt E; Chen A; Kanagawa O; Sharpe A; Mathis D; Benoist C. 2003. Paradoxical dampening of anti-islet self-reactivity but promotion of diabetes by OX40 ligand. J Immunol 171(12):6954-60. [PubMed: 14662903] [MGI Ref ID J:86926]
Chen AI; McAdam AJ; Buhlmann JE; Scott S; Lupher ML Jr; Greenfield EA; Baum PR; Fanslow WC; Calderhead DM; Freeman GJ; Sharpe AH. 1999. Ox40-ligand has a critical costimulatory role in dendritic cell:T cell interactions. Immunity 11(6):689-98. [PubMed: 10626891] [MGI Ref ID J:59203]
Tnfsf4tm1Shr relatedArestides RS; He H; Westlake RM; Chen AI; Sharpe AH; Perkins DL; Finn PW. 2002. Costimulatory molecule OX40L is critical for both Th1 and Th2 responses in allergic inflammation. Eur J Immunol 32(10):2874-80. [PubMed: 12355440] [MGI Ref ID J:169800]
Chappell CP; Draves KE; Giltiay NV; Clark EA. 2012. Extrafollicular B cell activation by marginal zone dendritic cells drives T cell-dependent antibody responses. J Exp Med 209(10):1825-40. [PubMed: 22966002] [MGI Ref ID J:191423]
Chen AI; McAdam AJ; Buhlmann JE; Scott S; Lupher ML Jr; Greenfield EA; Baum PR; Fanslow WC; Calderhead DM; Freeman GJ; Sharpe AH. 1999. Ox40-ligand has a critical costimulatory role in dendritic cell:T cell interactions. Immunity 11(6):689-98. [PubMed: 10626891] [MGI Ref ID J:59203]
Ekkens MJ; Liu Z; Liu Q; Whitmire J; Xiao S; Foster A; Pesce J; VanNoy J; Sharpe AH; Urban JF; Gause WC. 2003. The role of OX40 ligand interactions in the development of the Th2 response to the gastrointestinal nematode parasite Heligmosomoides polygyrus. J Immunol 170(1):384-93. [PubMed: 12496423] [MGI Ref ID J:127284]
Liu C; Lou Y; Lizee G; Qin H; Liu S; Rabinovich B; Kim GJ; Wang YH; Ye Y; Sikora AG; Overwijk WW; Liu YJ; Wang G; Hwu P. 2008. Plasmacytoid dendritic cells induce NK cell-dependent, tumor antigen-specific T cell cross-priming and tumor regression in mice. J Clin Invest 118(3):1165-75. [PubMed: 18259609] [MGI Ref ID J:135308]
Vu MD; Xiao X; Gao W; Degauque N; Chen M; Kroemer A; Killeen N; Ishii N; Chang Li X. 2007. OX40 costimulation turns off Foxp3+ Tregs. Blood 110(7):2501-10. [PubMed: 17575071] [MGI Ref ID J:147020]
Animal Health Reports
Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.Colony Maintenance
Diet Information LabDiet® 5K52/5K67
| Pricing for USA, Canada and Mexico shipping destinations |
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Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $2450.00 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.
Embryos
Price (US dollars $) Frozen Embryo $1600.00 Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Supply Notes
- Cryopreserved Embryos
Available to most shipping destinations1
This strain is also available as cryopreserved embryos2. Orders for cryopreserved embryos may be placed with our Customer Service Department. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos, please visit our Cryopreserved Embryos web page.
1 Shipments cannot be made to Australia due to Australian government import restrictions.
2 Embryos for most strains are cryopreserved at the two cell stage while some strains are cryopreserved at the eight cell stage. If this information is important to you, please contact Customer Service.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 Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $3185.00 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.
Embryos
Price (US dollars $) Frozen Embryo $2080.00 Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Supply Notes
- Cryopreserved Embryos
Available to most shipping destinations1
This strain is also available as cryopreserved embryos2. Orders for cryopreserved embryos may be placed with our Customer Service Department. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos, please visit our Cryopreserved Embryos web page.
1 Shipments cannot be made to Australia due to Australian government import restrictions.
2 Embryos for most strains are cryopreserved at the two cell stage while some strains are cryopreserved at the eight cell stage. If this information is important to you, please contact Customer Service.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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Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
| Control | ||
|---|---|---|
| 001976 NOD/ShiLtJ | ||
| Considerations for Choosing Controls | ||
| Control Pricing Information for Genetically Engineered Mutant Strains. | ||
| phone: | 207-288-6470 |
| fax: | 207-288-6655 |
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