S1P是机体重要的脂质信号分子，通过细胞外或细胞内途径发挥功能。EOB（eye-open at birth）是一种眼睑发育障碍，同时也是一个重要的动物模型，其所揭示的规律对皮肤伤口愈合及肿瘤细胞迁移具有重要的指导作用。SPNS2是最近发现的一种S1P的转运体，SPNS2突变造成血中S1P水平降低，影响淋巴细胞迁移和血管发生。我们发现并鉴定一种Spns2突变大鼠，其EOB的发生率为100%。预实验研究发现：胚胎阶段给予S1P或EGFR的配体可以挽救SPNS2突变大鼠的EOB表型；SPNS2突变的角质细胞中缺乏肌动蛋白应力纤维，提示：SPNS2转运S1P在角质细胞迁移过程中发挥重要作用，并且EGFR信号通路可能参与其间。本课题拟利用该SPNS2突变大鼠EOB模型，采用组织培养和细胞培养的方法，详细阐明SPNS2转运S1P影响角质细胞迁移的分子机制，为今后以SPNS2为靶点的临床应用奠定基础。

Sphingosine 1-phosphate is a critical lipid mediator regulates diverse cellular processes through the extracellular or intracellular signal pathways. EOB (eye-open at birth) is a phenotype of deficiency in eyelid development. In fact, EOB is also an important animal model from which the mechanism elucidated is similar to healing of skin and migration of tumor. SPNS2 (Spinster homolog 2) is a transporter of S1P which was found in zebrafish recently. The mutation of SPNS2 causes the quite low concentration of S1P in plasma which inhibits the immune cell egressing and influences angiogenesis in animals. We have found a strain of rat in SPNS2 mutant which was caused by by exogenous EGFP insertion. This SPNS2 mutant rat displays the EOB phenotype in 100% penetration. Our preliminary experiments showed that administration of S1P or EGFR ligands can rescue the EOB phenotype with the uterus injection at E16.5. The keratinocyte in SPNS2 mutant showed the defect in the formation of actin stress fibers in vitro. These results suggest that SPNS2 mutant which causes the defect in S1P transport has the critical roles in migration of kerationocyte. In addition, this process might also include the EGFR signal pathway. In this project, we are planning to elucidate the molecular mechanism of SPNS2 in migration of keratinocyte using the EOB model in SPNS2 mutant rat in vivo and vitro, respectively. It will provide theoretical basis for the SPNS2 as a therapeutic targets in clinical application in near future.