A XENOPUS LAEVIS RESEARCH RESOURCE FOR IMMUNOBIOLOGY

描述（由申请人提供）：非洲爪蟾是研究免疫系统发育和个体发育的最佳变温脊椎动物模型之一。X.来自哺乳动物的laevis允许将物种特异性适应与免疫系统的更保守特征区分开。X. laevis提供了一种独特的、通用的非哺乳动物模型，用于研究在MHC限制性和非限制性识别、个体发育和生殖发育以及抗肿瘤、病毒和细菌的背景下的体液和细胞介导的免疫。特别是，发育调控收购的MHC I类分子在变态和容易与它可以实验操作胚胎和幼虫表达前的I类和其他成人特异性抗原允许一个解决的问题，MHC限制，自身免疫，和自我耐受的发展，不能很容易地在其他动物模型中研究。研究X。几十年来，由于对哺乳动物的研究，产生了许多宝贵的研究工具，包括MHC定义的同基因克隆和近交系动物、转基因系、细胞系、单克隆抗体和cDNA探针，这些工具需要保存、富集并提供给科学界。因此，这一更新建议的总体目标是保护、促进和进一步发展X。作为一般生物医学研究，特别是免疫学研究的重要模型。一如原来的建议，建议的两个主要目的是：（1）维持、改善和宣传我们的X。通过继续保持和提高我们资源的性能和质量;通过提供动物，非商业可用，并应要求提供试剂;通过协助，培训和告知科学家和学生有关X。laevis;以及通过网站传播信息、做广告和与科学界互动。(2)开发新的实验动物、方法和试剂，通过产生新的同基因克隆MHC和小H抗原的集合;通过适应转基因技术和产生转基因，其是同基因克隆，在淋巴组织中表达荧光报告基因（例如，胸腺、脾）或白细胞;通过使用转基因通过RNA干扰开发体内敲低以揭示免疫相关基因的功能;以及通过产生新的X. LAEVIS特异性抗体（Ab）识别免疫相关分子。 相关性：此次更新申请的总体目标是保护和促进非洲爪蟾作为一般生物医学研究，特别是免疫学研究的重要非哺乳动物比较模型。我们建议继续维护和发展这一独特的非哺乳动物资源设施，用于生物医学研究，以造福整个科学界。

DESCRIPTION (provided by applicant): Xenopus laevis is one of the best ectothermic vertebrate models for studying the phylogeny and ontogeny of the immune system. The evolutionary distance of X. laevis from mammals permits distinguishing species-specific adaptations from more conserved features of the immune system. X. laevis, provides a unique, versatile, non-mammalian model with which to study humoral and cell-mediated immunity in the context of MHC restricted and unrestricted recognition, ontogeny, and phylogeny, and against tumors, viruses, and bacteria. In particular, the developmentally regulated acquisition of MHC class I molecules during metamorphosis and the ease with which one can experimentally manipulate embryos and larvae prior to expression of class I and other adult-specific antigens allows one to address questions about MHC restriction, autoimmunity, and the development of self-tolerance that can not be easily studied in other animal models. Studies with X. laevis over several decades have resulted in the generation of many invaluable research tools including MHC-defined isogenetic clones and inbred strains of animals, transgenic lines, cell lines, monoclonal antibodies, and cDNA probes that need to be preserved, enriched and made available to the scientific community. The broad objective of this renewal proposal, therefore, is to safeguard, promote and further develop X. laevis as an important model for biomedical research in general, and immunology, in particular. As in the original proposal, two major aims are proposed: (1) Maintenance, improvement and advertisement of our X. laevis facility by continuing to maintain and improve the performance and quality of our resource; by providing animals, not commercially available, and reagents upon request; by assisting, training, and informing scientists and students about X. laevis; and by disseminating information, advertising and interacting with the scientific community through a web site. (2) Development of new experimental animals, methodologies, and reagents by producing a new collection of isogenetic clones MHC and minor-H-antigen defined; by adapting transgenesis techniques and generating transgenic, which are isogenetic clones, expressing fluorescent reporter genes in lymphoid tissues (e.g., thymus, spleen) or leukocytes; by developing in vivo knockdown by RNA interference using transgenesis to reveal the function of immunologically-relevant genes; and by generating new X. laevis-specific antibodies (Abs) recognizing immunologically-relevant molecules. RELEVANCE: The overall objective of this renewal application is to safeguard and promote the frog Xenopus laevis, as an important non-mammalian comparative model for biomedical research in general, and immunology, in particular. We are proposing to continue the maintenance and the development of this unique non-mammalian resource facility for biomedical research for the benefit of the whole scientific community.