The Maternal/Fetal Interaction

母体/胎儿的相互作用

• 批准号: 7169609
• 负责人: EDWARD E SCHMIDT
• 金额: $ 33.03万
• 依托单位: MONTANA STATE UNIVERSITY - BOZEMAN
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-02-01 至 2010-01-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7169609
• 关键词: Adult; Affect; Amino Acids; Biological Models; Cell Nucleus; Cells; Chronic; Common iliac lymph node; Communication; DNA-Directed RNA Polymerase; Defect; Exhibits; Family; Fetus; Gene Expression; Gene Family; Genes; Genetic Transcription; Immune; Immune system; Lead; Maternal-Fetal Exchange; Mediating; Methods; Mothers; Mus; Mutation; Placenta; Predisposition; Pregnancy; Pregnancy Outcome; Proteins; Rag1 Mouse; Rate; Regulator Genes; Role; Side; Signal Transduction; Site; Spontaneous abortion; Standards of Weights and Measures; TATA-Box Binding Protein; Testing; Tissues; embryo tissue; fetal; fetus cell; implantation; mutant; new technology; novel; novel therapeutics; prognostic; tool

DESCRIPTION (provided by applicant): We have developed a line of mice bearing a targeted mutation in the TATA-binding protein (TBP) that replaces the endogenous gene with a version that is identical except it produces a protein lacking 111 of the first 135 amino acids of the protein. Adult mice homozygous for this mutation (tbp ^N/^N are normal; however mutant fetuses suffer a very high rate of immune-mediated mid gestational miscarriages. We can rescue the mutants past this crisis in various ways, including: 1) providing them with wildtype extra embryonic tissues; 2) rearing them in severely immune compromised dams; or 3) disrupting fetal (2m expression in their placentas. Thus, these mice provide an important model system for studying both the fetal and the maternal side of the maternal/fetal immune interaction. We hypothesize that the maternal/fetal immune interaction involves the interplay between maternal immune cells and fetal genes expressed at the maternal/fetal interface in the placenta; alteration of either maternal or fetal players in this interaction can affect the outcome of pregnancy. In this study, we propose three Specific Aims: Aim 1, identify the cellular components of the maternal immune system that participate in rejection of tbp^N/^N fetuses; Aim 2, characterize expression of MHC-I family genes at the implantation sites of tbp+/+, tbp^N/+, and tbp^N/^N fetuses; and Aim 3, identify proteins that interact with the TBP N-terminus in placenta. Results obtained under Specific Aim 1 should reveal maternal factors that can compromise pregnancy. Results obtained under Specific Aim 2 are expected to reveal fetal gene expression defects that might compromise pregnancy. Discoveries made under Aims 1 and 2 could lead to novel therapeutic strategies for combating chronic miscarriages. Finally, results obtained under Specific Aim 3 are expected to reveal gene regulatory mechanisms that underlie expression defects which can compromise pregnancy. These results could lead to novel prognostic tools for predicting susceptibility to spontaneous miscarriages.

描述（由申请人提供）：我们已经开发了一系列在塔塔结合蛋白（TBP）中带有靶向突变的小鼠，该蛋白（TBP）用一种相同的版本代替了内源基因，除了它产生了蛋白质的第135个氨基酸的蛋白质，而蛋白质缺乏蛋白质。成年小鼠纯合为此突变（TBP ^n/ ^n是正常的；但是突变的胎儿的免疫介导的妊娠中期流产的速度很高。我们可以以各种方式拯救过这种危机的突变体，包括：1）为它们提供野生型额外的胚胎组织； 2）在严重免疫受损的大坝中饲养它们；或3）破坏胎儿（其胎盘中的2m表达。因此，这些小鼠提供了一个重要的模型系统，用于研究胎儿/胎儿免疫相互作用的胎儿和孕妇侧。我们假设，孕产妇/胎儿的免疫相互作用涉及在母体/胎儿相互作用在母体相互作用的相互作用的相互作用在母体/胎儿相互作用的相互作用;在母体/胎儿相互作用的相互作用;妊娠的结果。在特定目标下获得的胎盘中的TBP N末端应揭示可能损害妊娠的母体因素。根据目标1和2进行的发现可能会导致对抗慢性流产的新型治疗策略。最后，有望在特定目标3下获得的结果揭示基因调节机制，这些机制是表达缺陷的基础，这些缺陷可能会损害妊娠。这些结果可能会导致新的预后工具，以预测自发流产的易感性。