B6N.129S6-Sphk1^tm1Rlp/J

Stock number: 019095
Product name: Sphk1-
Strain synonyms: SK1-, Sphk1 KO
Research areas: Apoptosis Research, Cell Biology Research, Immunology, Inflammation and Autoimmunity Research

Description

These Sphk1 KO mice may be useful for studying role of sphingosine-1-phosphate (S1P) in cell survival and proliferation.

 

Detailed description

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.

Development

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

Symbol: Sphk1^tm1Rlp
Name: targeted mutation 1, Richard L Proia
MGI accession ID: MGI:3526071
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Sphk1
Marker name: sphingosine kinase 1
Chromosome: 11
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.