A XENOPUS LAEVIS RESEARCH RESOURCE FOR IMMUNOBIOLOGY

爪蟾免疫生物学研究资源

• 批准号: 6764873
• 负责人: JACQUES Robert
• 金额: $ 27.32万
• 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/6764873
• 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）：长期以来，已成功将Laevis用作研究复杂免疫系统的系统发育的选择。此外，X. laevis已被证明是一个出色的模型系统，用于回答不限于给定分类群的基本免疫学问题。在某种程度上，这是因为爪蟾免疫系统的发展发生在两次不同的时间：在幼虫寿命中，然后在从免疫能力幼虫到免疫能力的成年的变质过渡期间再次发生。 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). 此外，变形是荷尔蒙驱动的，可以检查发育中的免疫系统中与免疫学相关的神经内分泌 - 免疫系统相互作用。爪蟾免疫学的另一个关键方面使其作为模型的重要性很重要，这是据记录在前的幼体幼虫时期的经典和非经典MHC I类表达。最后，表达或缺乏MHC I类和II分子的可移植肿瘤细胞系也有助于将Xenopus用作自然存在的“敲除”物种。该提案的广泛目标是通过以下方式进一步发展为非哺乳动物免疫生物学的模型，通过：（1）确保Xenopus的不同克隆，菌株和种类的系统繁殖和饲养； （2）组织信息和现有研究材料的中央存储库（例如，细胞系，DNA库，mAb，动物，动物）很容易为科学界使用； （3）生成用于免疫研究的新工具（例如，新的mAb，cDNA库，细胞线，转基因青蛙）。现有研究的许多领域应该受益于满足这些目标。我们设想：X. laevis的进一步发展为：一种用于研究的非哺乳动物模型：（1）肿瘤免疫； （2）个体发育过程中的自我耐受性和自身免疫性； （3）宿主 - 病原体相互作用； （4）基因组进化和基因组调节； （5）免疫毒理学（例如内分泌破坏者）； （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）免疫中收费表格（结构和功能）的演变。