ROLE OF TUMOR NECROSIS FACTOR-ALPHA IN DEVELOPMENT

描述(改编自《调查者摘要》)：远景目标 本研究的目的是明确肿瘤坏死因子基因家族在肿瘤坏死因子基因中的作用(S) 繁殖。新的实验方法已经被开发出来 评估滋养层细胞TNFa功能的目的包括 利用携带TNFa/LTA和肿瘤坏死因子缺失的基因敲除(KO)小鼠 肿瘤坏死因子受体基因与小鼠滋养层细胞系的建立 来自这些小鼠和正常小鼠。初步实验表明：1) 肿瘤坏死因子信号系统对胎盘的正常发育至关重要 2)肿瘤坏死因子/肿瘤坏死因子受体信号转导途径与性别相关 影响正常发育的，3)滋养层细胞系 小鼠胎盘表达TNFa基因，4)在某些条件下， 滋养层细胞系的生长受到外源TNFa的抑制。其他内容 研究表明，肿瘤坏死因子的另外两个生物强效成员 超家族FasL和lt-β在子宫和胎盘中表达 怀孕的小鼠，初步数据强烈表明FasL具有 活化在限制母胎迁移中的重要作用 造血细胞。

DESCRIPTION (Adapted from the Investigator's Abstract): The long range goal of this research is to define the role(s) of the TNF gene family in reproduction. New experimental approaches have been developed for the purpose of evaluating the functions of trophoblast cell TNFa that include use of knockout (KO) mice carrying deletions of the TNFa/LTa and TNF receptor (TNF-R) genes, and generation of mouse trophoblastic cell lines from these as well as normal mice. Preliminary experiments show that: 1) the TNF signaling system is critical to normal development of placental compartments, 2) TNF/TNF-R signaling is involved in gender-specific pathways that affect normal development, 3) trophoblastic cell lines derived from mouse placentas express the TNFa gene and, 4) under some conditions, trophoblastic cell lines are growth-inhibited by exogenous TNFa. Additional studies demonstrate that two other biologically-potent members of the TNF superfamily, FasL and Lt-beta, are expressed in the uteri and placentae of pregnant mice, and preliminary data strongly suggest that FasL has an important role in restricting maternal-fetal migration of activated hematopoietic cells.