Sphingosine Kinase 1 (Sphk1) Knockout Mouse for Utilization in Developmental Biology

This technology includes a sphingosine kinase 1 (Sphk1) knockout mouse model for use in developmental biology research. Sphingosine-1-phosphate (S1P) is synthesized from sphingosine and ATP by the action of sphingosine kinase, and activates cell signaling. Two sphingosine kinases, SPHK1 and SPHK2, have been identified. To study the physiological function of SPHK1, Sphki null mice were generated. The mice were viable, fertile, with no obvious abnormalities. Total SPHK activity in most tissues was substantially reduced, suggesting the presence of other sphingosine kinases. Some reduction in S1P levels was observed in tissues, but a more significant decrease was observed in serum. Neither vascular development nor lymphocyte distribution were affected in Sphki-/- mice. Sphingosine kinase also phosphorylates and activates the immunosuppressant drug FTY720. FTY720 was phosphorylated and elicited lymphopenia in the Sphki null mice, suggesting that some key activities that require S1P receptor signaling can occur in the absence of SPHK1. The mice with the gene for sphingosine kinase 1 deleted will be valuable in determining the functions of sphingosine phosphate and S1P1 receptors.