| 216892 |
Q91VM4 |
SPNS2_MOUSE |
Sphingosine-1-phosphate transporter SPNS2 (Protein spinster homolog 2) (Spinster homolog 2) (Spns2) |
DISRUPTION PHENOTYPE |
Deficient mice are viable, do not exhibit cardiac defects or embryonic lethality, and are generally normal and fertile (PubMed:22664872, PubMed:22406534). Deficient mice have decreased levels of sphingosine 1-phosphate (S1P) and dihydro-S1P in blood, accompanied by increases in very long chain ceramide species, and have defective lymphocyte trafficking (PubMed:22664872, PubMed:22406534, PubMed:23180825). S1P levels are increased in lymph from deficient mice as well as in specific tissues, including lymph nodes, and interstitial fluid (PubMed:23180825). Moreover, these mice have aberrant lymphatic sinus that appeared collapsed, with reduced numbers of lymphocytes (PubMed:23180825). Mice display marked accumulation of mature T-cells in thymus and decreased numbers of peripheral T-cells in blood and secondary lymphoid organs (PubMed:22406534, PubMed:34260944). Mature recirculating B-cells are reduced in frequency in the bone marrow as well as in blood and secondary lymphoid organs (PubMed:22406534). Mice do not show defects in S1P release from blood cells (PubMed:22406534). Knockout mice are protected against experimental autoimmune encephalomyelitis (PubMed:34260944). Mutants also show a profound hearing impairment, characterized by a progressive degeneration of sensory hair cells in the organ of Corti (PubMed:25356849, PubMed:30973865). Hearing loss is caused by a decline in the endocochlear potential (PubMed:25356849). Conditional deletion in the cochlea causes early onset progressive hearing loss (PubMed:25356849). In contrast, hearing impairment is not observed in mice with targeted deletion in red blood cells, platelets, lymphatic or vascular endothelial cells (PubMed:25356849). {ECO:0000269|PubMed:22406534, ECO:0000269|PubMed:22664872, ECO:0000269|PubMed:23180825, ECO:0000269|PubMed:25356849, ECO:0000269|PubMed:30973865, ECO:0000269|PubMed:34260944}. |