These Sphk1 KO mice may be useful for studying role of sphingosine-1-phosphate (S1P) in cell survival and proliferation.
Richard L Proia, National Institutes of Health
A neo cassette replaces exons 3-5 and part of exon 6, encoding the lipid kinase catalytic domain and putative nucleotide binding motif, of the sphingosine kinase 1 (Sphk1) gene, abolishing gene function. SPHK1, expressed in many cell types, is an enzyme that catalyzes the synthesis of sphingosine-1-phosphate (S1P), a lipid signaling molecule, from sphingosine and ATP. S1P regulates immune cell trafficking and vascular function. Mice homozygous for this allele are viable and fertile. SPHK1 KO mice exhibit delayed histamine clearance and severe hypotension during anaphylaxis.
A targeting vector was designed to replace exons 3-5 and part of exon 6 encoding the sphingosine kinase 1 (Sphk1) gene with a neomycin resistance (neo). The construct was electroporated into 129S6/SvEvTac-derived TC1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and the resulting chimeric males were bred to C57BL/6NCrl. These mice were backcrossed to C57BL/6NCrl mice for at least 7 generations. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6NJ (Stock No. 005304) for at least one generation to establish the colony.
|Allele Name||targeted mutation 1, Richard L Proia|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||SK1-; SphK1 KO; Sphk1-|
|Gene Symbol and Name||Sphk1, sphingosine kinase 1|
|Strain of Origin||129S6/SvEvTac|
|Molecular Note||A neo replaced exons 3-5 and the 5' end of exon 6, deleting sequence corresponding to the putative lipid kinase catalytic domain, which contains the conserved domains C1, C2, C3 and part of C4, and a putative nucleotide binding motif. Absence of mRNA was demonstrated in kidney samples by Northern blot and RT-PCR analyses.|
|Mutations Made By|| |
Richard Proia, National Institutes of Health
When maintaining a live colony, homozygous mice may be bred together.
When using the Sphk1- mouse strain in a publication, please cite the originating article(s) and include JAX stock #019095 in your Materials and Methods section.