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 NOD.129S6(B6)-S1pr1tm2Rlp/JbsJ    (Changed: 20-SEP-12 ) Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Mating System +/+ sibling x Heterozygote         (Female x Male)   29-JUL-10 Species laboratory mouse Background Strain NOD Donor Strain 129S6/SvEvTac   Donating Investigator Dr. Jeffrey A. Bluestone,   University of California, San Francisco

Description
These S1pr1^loxP/loxP mice possess loxP sites flanking exon 2 of the sphingosine-1-phosphate receptor 1 (S1pr1) gene. A floxed-neo cassette is still present downstream of exon 2. S1PR1 is a G protein-coupled receptor for lysophospholipid sphingosine-1-phosphate (S1P) and is highly expressed in endothelial cells. S1PR1 is essential for vascular maturation during embryonic development and is also involved in cell survival, migration, adhesion, and proliferation. This receptor plays a role in the regulation of innate and adaptive immune responses by controlling lymphocyte egress from the thymus, spleen, bone marrow, and lymph nodes. It has also been implicated in tumor angiogenesis and metastasis. Mice that are homozygous for this allele are viable and fertile. When these mutant mice are bred to mice that express Cre recombinase, resulting offspring will have exon 2 deleted in cre-expressing tissues.

For example, when crossed to B6.Cg-Tg(Tek-cre)1Ywa/J (Stock No. 008863) Mice expressing Cre recombinase in vascular endothelial cells during embryogenesis and adulthood, the resulting offspring die by E14.5 due to muscle defects including heart, vascular smooth muscle, and skeletal muscle defects.

Incidence studies performed at The Jackson Laboratory shows that NOD congenic mutant mice are diabetes suppressed (females 15% and 15% of males at 23 weeks of age). Fine mapping of this stock indicates that the congenic region (D3Mit189, 100Mb through D3Mit199, 123Mb) spans the Idd 10/18 region on Chromosome 3. The diabetes incidence of this stock is similar to NOD.B6-Idd10/18 (D3Mit190, 98Mb through D3Mit315, 115Mb), Stock No. 013186. Therefore, it is highly likely that the diabetes resistance observed is attributable to donor 129 strain-linked resistance alleles at these known B6 and 129 resistance loci on Chr. 3.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development
A targeting vector was designed to insert a single loxP site upstream of exon 2, and a loxP-flanked neomycin resistance (neo) cassette downstream of exon 2 of the sphingosine-1-phosphate receptor 1 (S1pr1) gene. The construct was electroporated into 129S6/SvEvTac-derived TC1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6NCrl blastocysts and resulting chimeric males were bred with C57BL/6NCrl females. These mice were bred to NOD mice for at least 10 generations. Upon arrival, mice were bred to NOD/ShiLtJ inbred mice (Stock No. 001976) for at least one generation to establish the colony.

Control Information

	Control
	Wild-type from the colony
	001976 NOD/ShiLtJ	(approximate)
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of S1pr1

021017	B6.129P2-S1pr1tm1.1Cys/J
019141	B6N.129S6(FVB)-S1pr1tm2.1Rlp/J

View Strains carrying other alleles of S1pr1     (2 strains)

Additional Web Information

Introduction to Cre-lox technology

Phenotype

Phenotype Information

View Research Applications

Research Applications

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

Cardiovascular Research

Research Tools
Cre-lox System
      loxP-flanked Sequences
Diabetes and Obesity Research
      loxP

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		S1pr1tm2Rlp
Allele Name		targeted mutation 2, Richard L Proia
Allele Type		Targeted (Floxed/Frt)
Common Name(s)		S1P1loxP; S1Pr1fl; S1pr1flox;
Mutation Made By		Richard Proia,   National Institutes of Health
Strain of Origin		129S6/SvEvTac
Gene Symbol and Name		S1pr1, sphingosine-1-phosphate receptor 1
Chromosome		3
Gene Common Name(s)		AI849002; CD363; CHEDG1; D1S3362; ECGF1; EDG-1; EDG1; Edg1; S1P; S1P1; endothelial differentiation sphingolipid G-protein-coupled receptor 1; endothelial differentiation spingolipid G-protein-coupled receptor 1; expressed sequence AI849002;
Molecular Note		Exon 2 was flanked by loxP sites, one upstream in the intron and two more downstream on both sides of an inserted neomycin selection cassette. These gene modifications did not disrupt the locus. [MGI Ref ID J:86450]

Genotyping

Genotyping Information

Genotyping Protocols

S1pr1^tm2Rlp, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Jeffreys AJ; Wilson V; Kelly R; Taylor BA; Bulfield G. 1987. Mouse DNA 'fingerprints': analysis of chromosome localization and germ-line stability of hypervariable loci in recombinant inbred strains. Nucleic Acids Res 15(7):2823-36. [PubMed: 3562240]  [MGI Ref ID J:8645]

Additional References

S1pr1^tm2Rlp related

Allende ML; Bektas M; Lee BG; Bonifacino E; Kang J; Tuymetova G; Chen W; Saba JD; Proia RL. 2011. Sphingosine-1-phosphate lyase deficiency produces a pro-inflammatory response while impairing neutrophil trafficking. J Biol Chem 286(9):7348-58. [PubMed: 21173151]  [MGI Ref ID J:170381]

Allende ML; Dreier JL; Mandala S; Proia RL. 2004. Expression of the sphingosine 1-phosphate receptor, S1P1, on T-cells controls thymic emigration. J Biol Chem 279(15):15396-401. [PubMed: 14732704]  [MGI Ref ID J:89522]

Allende ML; Tuymetova G; Lee BG; Bonifacino E; Wu YP; Proia RL. 2010. S1P1 receptor directs the release of immature B cells from bone marrow into blood. J Exp Med 207(5):1113-24. [PubMed: 20404103]  [MGI Ref ID J:161236]

Allende ML; Yamashita T; Proia RL. 2003. G-protein-coupled receptor S1P1 acts within endothelial cells to regulate vascular maturation. Blood 102(10):3665-7. [PubMed: 12869509]  [MGI Ref ID J:86450]

Allende ML; Zhou D; Kalkofen DN; Benhamed S; Tuymetova G; Borowski C; Bendelac A; Proia RL. 2008. S1P1 receptor expression regulates emergence of NKT cells in peripheral tissues. FASEB J 22(1):307-15. [PubMed: 17785606]  [MGI Ref ID J:134801]

Arnon TI; Xu Y; Lo C; Pham T; An J; Coughlin S; Dorn GW; Cyster JG. 2011. GRK2-dependent S1PR1 desensitization is required for lymphocytes to overcome their attraction to blood. Science 333(6051):1898-903. [PubMed: 21960637]  [MGI Ref ID J:176118]

Callen E; Faryabi RB; Luckey M; Hao B; Daniel JA; Yang W; Sun HW; Dressler G; Peng W; Chi H; Ge K; Krangel MS; Park JH; Nussenzweig A. 2012. The DNA damage- and transcription-associated protein paxip1 controls thymocyte development and emigration. Immunity 37(6):971-85. [PubMed: 23159437]  [MGI Ref ID J:191076]

Camprubi-Robles M; Mair N; Andratsch M; Benetti C; Beroukas D; Rukwied R; Langeslag M; Proia RL; Schmelz M; Ferrer Montiel AV; Haberberger RV; Kress M. 2013. Sphingosine-1-phosphate-induced nociceptor excitation and ongoing pain behavior in mice and humans is largely mediated by S1P3 receptor. J Neurosci 33(6):2582-92. [PubMed: 23392686]  [MGI Ref ID J:194273]

Chae SS; Paik JH; Allende ML; Proia RL; Hla T. 2004. Regulation of limb development by the sphingosine 1-phosphate receptor S1p1/EDG-1 occurs via the hypoxia/VEGF axis. Dev Biol 268(2):441-7. [PubMed: 15063179]  [MGI Ref ID J:92203]

Cinamon G; Zachariah MA; Lam OM; Foss FW Jr; Cyster JG. 2008. Follicular shuttling of marginal zone B cells facilitates antigen transport. Nat Immunol 9(1):54-62. [PubMed: 18037889]  [MGI Ref ID J:130200]

Deng J; Liu Y; Lee H; Herrmann A; Zhang W; Zhang C; Shen S; Priceman SJ; Kujawski M; Pal SK; Raubitschek A; Hoon DS; Forman S; Figlin RA; Liu J; Jove R; Yu H. 2012. S1PR1-STAT3 signaling is crucial for myeloid cell colonization at future metastatic sites. Cancer Cell 21(5):642-54. [PubMed: 22624714]  [MGI Ref ID J:189298]

Gaengel K; Niaudet C; Hagikura K; Siemsen BL; Muhl L; Hofmann JJ; Ebarasi L; Nystrom S; Rymo S; Chen LL; Pang MF; Jin Y; Raschperger E; Roswall P; Schulte D; Benedito R; Larsson J; Hellstrom M; Fuxe J; Uhlen P; Adams R; Jakobsson L; Majumdar A; VestweberD; Uv A; Betsholtz C. 2012. The sphingosine-1-phosphate receptor S1PR1 restricts sprouting angiogenesis by regulating the interplay between VE-cadherin and VEGFR2. Dev Cell 23(3):587-99. [PubMed: 22975327]  [MGI Ref ID J:189010]

Golan K; Vagima Y; Ludin A; Itkin T; Cohen-Gur S; Kalinkovich A; Kollet O; Kim C; Schajnovitz A; Ovadya Y; Lapid K; Shivtiel S; Morris AJ; Ratajczak MZ; Lapidot T. 2012. S1P promotes murine progenitor cell egress and mobilization via S1P1-mediated ROS signaling and SDF-1 release. Blood 119(11):2478-88. [PubMed: 22279055]  [MGI Ref ID J:182535]

Ishii M; Egen JG; Klauschen F; Meier-Schellersheim M; Saeki Y; Vacher J; Proia RL; Germain RN. 2009. Sphingosine-1-phosphate mobilizes osteoclast precursors and regulates bone homeostasis. Nature 458(7237):524-8. [PubMed: 19204730]  [MGI Ref ID J:147106]

Juarez JG; Harun N; Thien M; Welschinger R; Baraz R; Pena AD; Pitson SM; Rettig M; DiPersio JF; Bradstock KF; Bendall LJ. 2012. Sphingosine-1-phosphate facilitates trafficking of hematopoietic stem cells and their mobilization by CXCR4 antagonists in mice. Blood 119(3):707-16. [PubMed: 22049516]  [MGI Ref ID J:181661]

Jung B; Obinata H; Galvani S; Mendelson K; Ding BS; Skoura A; Kinzel B; Brinkmann V; Rafii S; Evans T; Hla T. 2012. Flow-regulated endothelial S1P receptor-1 signaling sustains vascular development. Dev Cell 23(3):600-10. [PubMed: 22975328]  [MGI Ref ID J:189009]

Kono M; Mi Y; Liu Y; Sasaki T; Allende ML; Wu YP; Yamashita T; Proia RL. 2004. The sphingosine-1-phosphate receptors S1P1, S1P2, and S1P3 function coordinately during embryonic angiogenesis. J Biol Chem 279(28):29367-73. [PubMed: 15138255]  [MGI Ref ID J:106055]

Ledgerwood LG; Lal G; Zhang N; Garin A; Esses SJ; Ginhoux F; Merad M; Peche H; Lira SA; Ding Y; Yang Y; He X; Schuchman EH; Allende ML; Ochando JC; Bromberg JS. 2008. The sphingosine 1-phosphate receptor 1 causes tissue retention by inhibiting the entry of peripheral tissue T lymphocytes into afferent lymphatics. Nat Immunol 9(1):42-53. [PubMed: 18037890]  [MGI Ref ID J:130407]

Lee H; Deng J; Kujawski M; Yang C; Liu Y; Herrmann A; Kortylewski M; Horne D; Somlo G; Forman S; Jove R; Yu H. 2010. STAT3-induced S1PR1 expression is crucial for persistent STAT3 activation in tumors. Nat Med 16(12):1421-8. [PubMed: 21102457]  [MGI Ref ID J:167520]

Liu G; Burns S; Huang G; Boyd K; Proia RL; Flavell RA; Chi H. 2009. The receptor S1P1 overrides regulatory T cell-mediated immune suppression through Akt-mTOR. Nat Immunol 10(7):769-77. [PubMed: 19483717]  [MGI Ref ID J:150139]

Liu G; Yang K; Burns S; Shrestha S; Chi H. 2010. The S1P(1)-mTOR axis directs the reciprocal differentiation of T(H)1 and T(reg) cells. Nat Immunol 11(11):1047-56. [PubMed: 20852647]  [MGI Ref ID J:166555]

Mair N; Benetti C; Andratsch M; Leitner MG; Constantin CE; Camprubi-Robles M; Quarta S; Biasio W; Kuner R; Gibbins IL; Kress M; Haberberger RV. 2011. Genetic evidence for involvement of neuronally expressed S1P receptor in nociceptor sensitization and inflammatory pain. PLoS One 6(2):e17268. [PubMed: 21359147]  [MGI Ref ID J:171085]

Mionnet C; Sanos SL; Mondor I; Jorquera A; Laugier JP; Germain RN; Bajenoff M. 2011. High endothelial venules as traffic control points maintaining lymphocyte population homeostasis in lymph nodes. Blood 118(23):6115-22. [PubMed: 21937697]  [MGI Ref ID J:179107]

Mok SW; Proia RL; Brinkmann V; Mabbott NA. 2012. B cell-specific S1PR1 deficiency blocks prion dissemination between secondary lymphoid organs. J Immunol 188(10):5032-40. [PubMed: 22504650]  [MGI Ref ID J:188671]

Montrose DC; Scherl EJ; Bosworth BP; Zhou XK; Jung B; Dannenberg AJ; Hla T. 2013. S1P(1) localizes to the colonic vasculature in ulcerative colitis and maintains blood vessel integrity. J Lipid Res 54(3):843-51. [PubMed: 23296878]  [MGI Ref ID J:194284]

Odumade OA; Weinreich MA; Jameson SC; Hogquist KA. 2010. Kruppel-like factor 2 regulates trafficking and homeostasis of gammadelta T cells. J Immunol 184(11):6060-6. [PubMed: 20427763]  [MGI Ref ID J:161230]

Olivera A; Eisner C; Kitamura Y; Dillahunt S; Allende L; Tuymetova G; Watford W; Meylan F; Diesner SC; Li L; Schnermann J; Proia RL; Rivera J. 2010. Sphingosine kinase 1 and sphingosine-1-phosphate receptor 2 are vital to recovery from anaphylactic shock in mice. J Clin Invest 120(5):1429-40. [PubMed: 20407207]  [MGI Ref ID J:161468]

Shoham AB; Malkinson G; Krief S; Shwartz Y; Ely Y; Ferrara N; Yaniv K; Zelzer E. 2012. S1P1 inhibits sprouting angiogenesis during vascular development. Development 139(20):3859-69. [PubMed: 22951644]  [MGI Ref ID J:187683]

You Y; Myers RC; Freeberg L; Foote J; Kearney JF; Justement LB; Carter RH. 2011. Marginal zone B cells regulate antigen capture by marginal zone macrophages. J Immunol 186(4):2172-81. [PubMed: 21257969]  [MGI Ref ID J:168986]

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	When maintaining a live colony, homozygous mice may be bred together.
Mating System	+/+ sibling x Heterozygote         (Female x Male)   29-JUL-10

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

General Supply Notes

• This strain is included in the Type 1 Diabetes Repository collection.

Control Information

	Control
	Wild-type from the colony
	001976 NOD/ShiLtJ	(approximate)
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

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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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