B6.129S6(FVB)-S1pr1^tm2.1Rlp/J

Stock number: 019141
Product name: S1P₁^loxP
Strain synonyms: S1Pr1, S1pr1
Research areas: Cancer Research, Cardiovascular Research, Developmental Biology Research, Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

These S1pr1^loxP/loxP mice possess loxP sites flanking exon 2. They may have applications in studies related to adaptive immune responses and vascular development.

Detailed description

These S1pr1^loxP/loxP mice possess loxP sites flanking exon 2 of the sphingosine-1-phosphate receptor 1 (S1pr1) gene. 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 the regulation of vascular function. 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.

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/6 blastocysts and resulting chimeric males were bred with C57BL/6NCrl females. Offspring, heterozygous for this S1pr1^loxP allele, were bred with B6.FVB-Tg(EIIa-cre)C5379Lmgd/J transgenic mice (Stock No. 003724) to delete the neo cassette. Resulting mice contained multiple gene rearrangments; intact floxed-exon 2, intact floxed-neo cassette, or excision of both exon 2 and the neo cassette. Progeny, containing only the floxed-exon 2, were crossed to remove the Cre-expressing transgene. The donating investigator reported that these mice were bred to C57BL/6NCrl mice for at least 7 generations (see SNP note below). Upon arrival, mice were bred to C57BL/6NJ inbred mice (Stock No. 005304) for at least one generation to establish the colony.

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, 3 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a C57BL/6J genetic background.

 

Allele

Symbol: S1pr1^tm2.1Rlp
Name: targeted mutation 2.1, Richard L Proia
MGI accession ID: MGI:5461228
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Marker symbol: S1pr1
Marker name: sphingosine-1-phosphate receptor 1
Chromosome: 3
Strain of origin: 129S6/SvEvTac
Molecular note: 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. Cre-mediated recombination removed the neo cassette and left exon 2 floxed.