Analysis of the Molecular Pathology for the Salidonmide Syndrome

萨利度胺是一种具有抗免疫和抗炎作用的药物。最近这种药被应用于几种疾病的治疗。然而，众所周知，对胚胎有很强的致畸作用，称为萨利度胺综合征，其机制尚不清楚。我们计划进行研究，以揭示沙利度胺致畸作用的机制。Roberts综合征是一种与salidomide综合征肢体表型相似的光秃表型的人类遗传病，我们对其进行了分子克隆。我们利用培养的细胞系分析了沙利度胺对可能靶基因表达水平的影响。我们发现ESCO2的表达抑制是Roberts综合征的缺陷，这可能提示salidomide综合征的部分机制。其他研究证实了罗伯茨病人淋巴细胞的细胞生物学特性。它们对丝裂霉素C比正常淋巴母细胞敏感，梭形检查点有问题。这些结果可能会揭示沙利度胺的副作用，并提示抑制其致畸作用的治疗方法

Salidomide is a medicine which has anti-immune effect and anti-inflamation effect. Recently this medicine is applied for the treatment for several diseases. However it is also well-known to show the strong teratogenic effect for the embryo which is called Salidomide syndrome, which mechanism is still unclear. We planed the research to disclose the mechanism of the teratogenic effect of the salidomide. We have experience the molecular cloning of Roberts syndrome which is human genetic disease with phenotype of phocomelia, which resemble to the limb phenotype of salidomide syndrome. We analyze the salidomide died on the expression level of possible target genes using cultured cell line. We found suppressed expression of ESCO2 which is defect in Roberts syndrome which might suggest the part of mechanism of salidomide syndrome. Other research effort proved the cellular biological characteristics of Roberts patient lymphoblasts. They are sensitive to the mitomycine C than normal lymphoblast and has problem in spindle checkpoint. These result might lead the disclosure of salidomide side effect and suggest the treatment to inhibit the teratogenic effect