This sphingosine-1-phosphate receptor 1 (S1pr1) floxed strain may be useful for studying S1pr1 signaling pathways in various cell types as it relates to autoimmune diabetes.
Dr. Jeffrey A. Bluestone, University of California, San Francisco
These S1pr1loxP/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.
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.
|Allele Name||targeted mutation 2, Richard L Proia|
|Allele Type||Targeted (Conditional ready (e.g. floxed), No functional change)|
|Allele Synonym(s)||S1P1loxP; S1Pr1fl; S1pr1flox|
|Gene Symbol and Name||S1pr1, sphingosine-1-phosphate receptor 1|
|Gene Synonym(s)||AI849002; CD363; CHEDG1; D1S3362; ECGF1; EDG-1; EDG1; Edg1; Edg1; S1P; S1P1; endothelial differentiation sphingolipid G-protein-coupled receptor 1; endothelial differentiation spingolipid G-protein-coupled receptor 1; expressed sequence AI849002|
|Strain of Origin||129S6/SvEvTac|
|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.|
|Mutations Made By|| |
Richard Proia, National Institutes of Health
|Please inquire about possible genotypes.|
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