A XENOPUS LAEVIS RESEARCH RESOURCE FOR IMMUNOBIOLOGY

爪蟾免疫生物学研究资源

• 批准号: 6894626
• 负责人: JACQUES Robert
• 金额: $ 23.4万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-06-01 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6894626
• 关键词: Xenopus; animal breeding; animal colony; biological models; biomedical facility; building /facility design /renovation; cell line; developmental immunology; genetic library; genetic registry /resource /referral center; genetic strain; genetically modified animals; monoclonal antibody

DESCRIPTION (provided by applicant): Xenopus laevis has long been used successfully as the ectothermic vertebrate species of choice for studying the phylogeny of the complex immune system. In addition, X. laevis has proved to be an excellent model system for answering fundamental immunological questions that are not phylogenetically restricted to a given taxon. In part, this is because development of the Xenopus immune system occurs at two distinct times: once during larval life, and then again during the metamorphic transition from immunocompetent larva to immunocompetent adult. Since the larval form is free-swimming and amenable to a variety of surgical and nonsurgical interventions, valuable information can be obtained that is not possible to obtain from in utero studies of mammals (e.g., development of self-tolerance to adult specific antigens, acquisition of a second T-cell repertoire, and ontogeny of T-cell subsets in a natural setting). Moreover, metamorphosis is hormonally driven which permits examination of immunologically relevant neuroendocrine-immune system interactions in a developing immune system. Another critical aspect of Xenopus immunology that makes it important as a model is the well-documented absence of classical and non-classical MHC class I expression during the pre-metamophic larval period. Finally, transplantable tumor cell lines that either express or lack MHC class I and II molecules also contribute to the use of Xenopus as a naturally-occurring "knockout" species. The broad objectives of this proposal are to further develop Xenopus laevis as a non-mammalian immunobiologically-focused model by: (1) assuring the systematic breeding and husbandry of different clones, strains, and species of Xenopus; (2) organizing a central repository of information and existing research materials (e.g., cell lines, DNA libraries, mAbs, animals) readily available to the scientific community; and (3) generating new tools for immunological research (e.g., new mAbs, cDNA libraries, cells lines, transgenics frogs). Many areas of existing and new research should benefit from satisfying these aims. We envision: further development of X. laevis as: a nonmammalian model for studying: (1) tumor immunity; (2) self-tolerance and autoimmunity during ontogeny; (3) host-pathogen interactions; (4) genome evolution and genomic regulation; (5) immunotoxicology (e.g. endocrine disruptors); (6) the role of heat shock proteins in immunity; (7) the function of nonclassical MHC class I antigens; and (8) the evolution of toll-like receptors (structure and function) in immunity.

描述（由申请人提供）：非洲爪蟾长期以来一直被成功地用作研究复杂免疫系统系统发育的变温脊椎动物物种。此外，X. laevis 已被证明是一个优秀的模型系统，可以回答基本的免疫学问题，这些问题在系统发育上不受特定分类单元的限制。在某种程度上，这是因为非洲爪蟾免疫系统的发育发生在两个不同的时期：一次是在幼虫生命期间，另一次是在从具有免疫能力的幼虫到具有免疫能力的成体的变态转变期间。由于幼虫形式是自由游泳的并且适合各种手术和非手术干预，因此可以获得从哺乳动物子宫内研究中不可能获得的有价值的信息（例如，对成体特异性抗原的自我耐受性的发展、获得第二个 T 细胞库的组成，以及自然环境中 T 细胞亚群的个体发育）。 此外，变态是由激素驱动的，这允许检查发育中的免疫系统中免疫学相关的神经内分泌-免疫系统相互作用。非洲爪蟾免疫学的另一个重要方面使其成为重要的模型，这是有据可查的在前变态幼虫时期经典和非经典 MHC I 类表达的缺失。最后，表达或缺乏 MHC I 类和 II 类分子的可移植肿瘤细胞系也有助于非洲爪蟾作为天然存在的“基因敲除”物种的使用。该提案的主要目标是通过以下方式进一步将非洲爪蟾开发为非哺乳动物免疫生物学模型：（1）确保不同克隆、品系和非洲爪蟾物种的系统育种和饲养； (2) 组织一个可供科学界随时获取的信息和现有研究材料（例如细胞系、DNA 文库、单克隆抗体、动物）的中央存储库； (3) 产生用于免疫学研究的新工具（例如新的单克隆抗体、cDNA 文库、细胞系、转基因青蛙）。现有和新研究的许多领域应该受益于满足这些目标。我们设想：将 X. laevis 进一步发展为：一种非哺乳动物模型，用于研究：（1）肿瘤免疫； (2)个体发育过程中的自我耐受和自身免疫； (3)宿主-病原体相互作用； (4) 基因组进化和基因组调控； (5) 免疫毒理学（如内分泌干扰物）； (6)热休克蛋白在免疫中的作用； (7)非经典MHC I类抗原的功能； （8）免疫中Toll样受体（结构和功能）的进化。