| 20397 |
Q8R0X7 |
SGPL1_MOUSE |
Sphingosine-1-phosphate lyase 1 (S1PL) (SP-lyase 1) (SPL 1) (mSPL) (EC 4.1.2.27) (Sphingosine-1-phosphate aldolase) |
DISRUPTION PHENOTYPE |
Mutant animals have a shortened lifespan (PubMed:21173151). Mutant mice show an increase of sphingoid base phosphates, but also other sphingolipids (including sphingosine, ceramide, and sphingomyelin) in the serum and/or liver, resulting in changes in the levels of serum and liver lipids not directly within the sphingolipid pathway, including phospholipids, triacyglycerol, diacylglycerol, and cholesterol (PubMed:20097939). They are deficient in B and T lymphocytes yet have high blood levels of neutrophils and monocytes along with elevated expression of pro-inflammatory cytokines. Their tissues are largely clear of infiltrating leukocytes and their neutrophils are defective in migration to chemotactic stimulus (PubMed:21173151). Mice lacking Sgpl1 exhibit complete podocyte foot process effacement and absence of slit diaphragms in kidney (PubMed:9464245, PubMed:28165339). They display hypoalbuminemia and an elevated urinary albumin/creatinine ratio (PubMed:28165339). They also display abnormal adrenal gland morphology and defective expression of enzymes involved in steroidogenesis in this tissue (PubMed:28165343). Conditional knockout in brain significantly reduces phosphoethanolamine levels with alterations in basal and stimulated autophagy involving decreased conversion of LC3-I to LC3-II, increased levels of lysosomal markers and aggregate-prone proteins such as APP and SNCA. Animals show profound deficits in cognitive skills (PubMed:28521611). {ECO:0000269|PubMed:20097939, ECO:0000269|PubMed:21173151, ECO:0000269|PubMed:28165339, ECO:0000269|PubMed:28165343, ECO:0000269|PubMed:28521611, ECO:0000269|PubMed:9464245}. |