These mice carry a mutation in the S1pr1 (sphingosine-1-phosphate receptor 1) gene that influences the migration of lymphocytes between the blood and tissues.
Jason Cyster, University of California San Francisco
Genetic Background | Generation |
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Allele Type | Gene Symbol | Gene Name |
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Targeted | S1pr1 | sphingosine-1-phosphate receptor 1 |
S1pr1 (sphingosine-1-phosphate receptor 1) is a Gi-coupled receptor expressed on the surface of lymphocytes. When it recognizes high levels of ligand (S1P) in the blood and lymph, egress of the cells from lymphoid organs into the blood is promoted. Downregulation or desensitization of this receptor enables lymphocytes to subsequently migrate from the blood into tissues.
The last 12 amino acids of the encoded protein carry a motif that is important for receptor desensitization following exposure to ligand. These mice carry a Thr-Ser-Ser (TSS) to Ala-Ala-Ala (AAA) mutation in this region that leads to a loss in sensitivity for ligand-mediated receptor down-modulation, leading to partial block in the desensitization process.
Mice are resistant to S1P-mediated S1PR1 internalization in naive T cells, follicular B cells and marginal zone (MZ) B cells. Augmented responses to S1P in chemotaxis assays and higher S1PR1 expression on MZ B cells are also seen. In addition, MZ B cells in mutant mice show abnormal distribution; they are confined to the marginal zone compartment and absent from the follicles. Mutant mice have normal numbers of naive T cells, follicular B cells and MZ B cells. Heterozygous and homozygous mutant mice show essentially the same phenotype.
A Thr-Ser-Ser (TSS) motif located in the C-terminus of the gene was substituted by Ala-Ala-Ala (AAA) through targeted mutation of 129P2/OlaHsd-derived E14 embryonic stem (ES) cells. A loxP-flanked neomycin resistance cassette was also inserted after the stop codon. The neomycin cassette was excised through crosses with B6.C-Tg(CMV-cre)1Cgn/J mice (see Stock No. 006054). Resultant animals were backcrossed to C57BL/6 for 7 generations by the donating lab.
Allele Name | targeted mutation 1.1, Jason G Cyster |
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Allele Type | Targeted |
Allele Synonym(s) | S1PR1TSS |
Gene Symbol and Name | S1pr1, sphingosine-1-phosphate receptor 1 |
Gene Synonym(s) | |
Promoter | S1pr1, sphingosine-1-phosphate receptor 1, mouse, laboratory |
Strain of Origin | 129P2/OlaHsd |
Chromosome | 3 |
Molecular Note | Nucleotide substitutions replaced the threonine and serines in the TxxSS motif in the last 12 amino acids of the sequence with alanines (p.T371A and p.(S374_S375delinsAA)). A floxP site flanked neomycin resistance gene cassette was inserted into the 3' UTR. Subsequent cre-mediated recombination removed the neo cassette. |
Homozygous mice may be bred together when breeding a live colony
When using the B6.129P2-S1pr1tm1.1Cys/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #021017 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous for S1pr1<tm1.1Cys> |
Frozen Mouse Embryo | B6.129P2-S1pr1<tm1.1Cys>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | B6.129P2-S1pr1<tm1.1Cys>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | B6.129P2-S1pr1<tm1.1Cys>/J Frozen Embryo | $3373.50 |
Frozen Mouse Embryo | B6.129P2-S1pr1<tm1.1Cys>/J Frozen Embryo | $3373.50 |
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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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
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