Description

Strain Information

Former Names NOD.Cg-Tnfsf4tm1Shr/DoiJ    (Changed: 17-DEC-04 ) Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Background Strain NOD Donor Strain 129S4 from J1 ES cell line H2 Haplotype g7 Generation N8F4+F5p (09-NOV-05)   Donating Investigator Christophe Benoist,   Joslin Diabetes Center

Appearance
pink-eyed albino
Related Genotype: A/? Tyr^c/Tyr^c

Description
Tnfsf4^tm1Shrhomozygous 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)-Tnfsf4^tm1Shr/DoiJ at generation N8F4.

Control Information

	Control
	001976 NOD/ShiLtJ
Considerations for Choosing Controls

Related Strains

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)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms

Diabetes Mellitus, Insulin-Dependent; IDDM - Models with phenotypic similarity to human disease where etiologies are distinct.2

2 Human genes are associated with this disease. Orthologs of those genes do not appear in the mouse genotype(s).

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Tnfsf4^tm1Shr/Tnfsf4^tm1Shr

        NOD.129S4-Tnfsf4^tm1Shr

• immune system phenotype
• decreased susceptibility to autoimmune diabetes (MGI Ref ID J:86926)
  • NOD mice homozygous for Tnfsf4^tm1Shr 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

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 and Inflammation Research
Autoimmunity (Type 1 Diabetes)

Genes & Alleles

Gene & Allele Information

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,   Brigham and Women's Hospital
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]

Genotyping

Genotyping Information

This strain will not have a genotyping protocol or one is not currently available.

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

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]

Additional References

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]

Tnfsf4^tm1Shr related

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]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Diet Information	LabDiet® 5K52/5K67

Purchasing information

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

Pricing

Supply Details

Standard Supply

Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.

Supply Notes

Cryopreserved Embryos This strain is also available as cryopreserved embryos from our Repository. Orders for cryopreserved embryos are supplied subject to a signed agreement that must be returned to the Customer Service Department after order placement. 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 from our repository, please visit our Cryopreserved Embryos web page. Cryorecovery - Standard. The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845. This strain is included in the Type 1 Diabetes Repository collection.

Control Information

	Control
	001976 NOD/ShiLtJ
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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Terms of Use

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General Terms and Conditions

Contact information

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

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