STUDIES OF ABNORMAL EMBRYONIC DEVELOPMENT

胚胎发育异常的研究

基本信息

批准号：
3312386
负责人：
CHRISTOPHER C LEUNG
金额：
$ 0.09万
依托单位：
LOUISIANA STATE UNIV HSC SHREVEPORT
依托单位国家：
美国
项目类别：
财政年份：
1979
资助国家：
美国
起止时间：
1979-07-01 至 1985-03-31
项目状态：
已结题

项目摘要

It has been well established that birth defects may be induced experimentally by heterologous antisera directed against certain tissue homogenates. The investigators isolated a glycoprotein from rat microvillar membrane and showed that rabbit antibodies to this glycoprotein antigen caused abnormal embryonic development. They are interested in the underlying mechanism whereby such specific antibodies can cause embryopathy. In order to delineate the mechanism of teratogenesis, the following projects will be performed: 1) production of monoclonal antibodies to the glycoprotein, 2) purification of aminopeptidase M from brush-border membrane, 3) identification of the antigenic peptides by protein blotting, 4) identification of the antigen by histochemical staining method, 5) studies of antigen distribution in various tissues by indirect immuno-peroxidase technique, 6) production of auto- or alloantibodies in pregnant rats, 7) ultrastructural localization of teratogenic IgG in vivo, 8) studies of ultrastructural changes in the visceral yolk-sac endoderm after teratogenic antibody administration, 9) studies of the effects of teratogenic IgG on visceral yolk-sac pinocytic uptake of macromolecules in vitro, 10) kinetic studies of immunoinhibition of aminopeptidase M activity and survival of visceral yolk-sac endodermal cells in culture, 11) studies of effects of teratogenic IgG on visceral yolk-sac release of N-acetylglucosaminidase and toxic oxygen metabolites, 12) studies of effects of teratogenic IgG on macrophage functions. The long-term objective of these proposed projects is to delineate the mechanism of teratogenesis induced by heterologous brush-border membrane antibodies.

已经很好地确定可以诱发先天缺陷通过针对某些组织的异源抗血清实验匀浆。研究人员将糖蛋白与大鼠分离微绒毛膜，表明对这种糖蛋白的兔抗体抗原引起异常的胚胎发育。他们对这种特定抗体可能导致的基本机制胚胎病。为了描述变质的机理，将执行以下项目：1）产生单克隆糖蛋白的抗体，2）从中纯化氨基肽酶M 刷膜膜，3）鉴定抗原肽蛋白质印迹，4）通过组织化学鉴定抗原染色方法，5）研究各种组织中抗原分布的研究间接免疫过氧酶技术，6）产生自动或自动或怀孕大鼠的同种抗体，7）致死性IgG体内，8）研究超微结构变化的研究染色性抗体给药后内脏蛋黄 - 萨克内胚层，9）致畸性IgG对内脏蛋黄-SAC-生物细胞的影响的研究体外大分子的摄取，10）免疫抑制的动力学研究氨基肽酶M的活性和内脏蛋黄 - 萨克内皮层的生存培养细胞，11）致畸性IgG对内脏的影响的研究 N-乙酰基葡萄糖胺酶和有毒氧代谢产物的蛋黄-SAC释放， 12）致畸性IgG对巨噬细胞功能的影响。这这些拟议项目的长期目标是描述由异源刷子膜诱导的致膜病的机理抗体。