A Sphingosine kinase 1 (Sphk1) knockout mouse
Sphingosine kinase 1 and 2 are enzymes that produce sphingosine-1-phosphate (S1P), a potent bioactive compound that activates a family of G-protein coupled receptors known as S1P receptors. Triggering these receptors on cells has important effects related to inflammation, immunity, cancer, angiogenesis, cell proliferation, adhesion, cardiovascular function, nervous system function and injury responses. Sphingosine kinase 1 is the predominant isozyme for extracellular S1P production. Sphingosine kinase 2 is the predominant isozyme that activates Fingolimod (brand name: Gilenya™), an immunomodulating drug that has been approved by the FDA for treating multiple sclerosis. The sphingosine kinase 1 knockout mouse and the sphingosine kinase 2 knockout mouse will be valuable for determining the functions of sphingosine-1- phosphate and S1P receptors. These mice will also be useful for the study of Fingolimod and related compounds.