A XENOPUS LAEVIS RESEARCH RESOURCE FOR IMMUNOBIOLOGY

爪蟾免疫生物学研究资源

• 批准号: 7915154
• 负责人: JACQUES Robert
• 金额: $ 11.32万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7915154
• 关键词: Address; Adult; Advertisements; Advertising; Animal Model; Animals; Antibodies; Antigens; Autoimmunity; Bacteria; Bacteriophage M13; Biological Metamorphosis; Biological Models; Biomedical Research; Cell Line; Cellular Immunity; Collection; Communities; Complex; Development; Embryo; Frequencies; Gene Transfer Techniques; Generations; Genes; Growth; Health; Histocompatibility; Histocompatibility Antigens Class I; Hybridomas; Hybrids; Immune system; Immunization; Immunobiology; Immunoglobulin Fragments; Immunology; Inbred Strains Animals; Integrase; Laboratories; Larva; Leukocytes; Libraries; Lymphoid Tissue; MHC Class I Genes; Maintenance; Mammals; Mediating; Methodology; Minor; Mixed Lymphocyte Culture Test; Modeling; Monoclonal Antibodies; Oncogenic Viruses; Performance; Phylogeny; Principal Investigator; Proteins; Protocols documentation; RNA Interference; Rana; Reagent; Recombinant Proteins; Reporter Genes; Research; Resources; Scientist; Self Tolerance; Skin Transplantation; Skin graft; Sleeping Beauty; Spleen; Staging; Students; Study models; T-Cell Receptor; T-Lymphocyte; Techniques; Thymus Gland; Training; Transgenic Organisms; Transposase; Update; Xenopus laevis; animal cloning; bacterial H antigen; cDNA Probes; comparative; improved; in vivo; interest; novel; positional cloning; tool; tumor; web site

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.

描述(申请人提供)：非洲爪哇是研究免疫系统的系统发育和个体发育的最好的外温脊椎动物模型之一。莱氏X.laevis与哺乳动物的进化距离允许区分物种特有的适应与更保守的免疫系统特征。莱维氏X.laevis提供了一种独特的、通用的非哺乳动物模型，用于在MHC限制性和非限制性识别、个体发育和系统发育以及针对肿瘤、病毒和细菌的背景下研究体液免疫和细胞免疫。特别是，在变态过程中发育调节的MHC I类分子的获得，以及在表达I类和其他成体特异性抗原之前，人们可以轻松地在实验中操纵胚胎和幼虫，这使得人们能够解决在其他动物模型中不容易研究的MHC限制、自身免疫和自我耐受的发展问题。几十年来对莱维氏X.laevis的研究已经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亲交配的动物品系、转基因品系、细胞系、克隆抗体和cDNA探针，这些工具需要保存、丰富并提供给科学界。因此，这项更新建议的广泛目标是维护、促进和进一步发展莱氏X.laevis作为一般生物医学研究，特别是免疫学的重要模式。与最初的提案一样，我们提出了两个主要目标：(1)通过继续保持和改进我们资源的性能和质量，维护、改进和宣传我们的莱氏X.laevis设施；通过应要求提供非商业用途的动物和试剂；通过协助、培训和告知科学家和学生关于X.laevis的信息；以及通过网站传播信息、广告和与科学界互动。(2)开发新的实验动物、方法和试剂，通过产生新的定义的同源克隆MHC和Minor-H抗原；通过采用转基因技术和产生在淋巴组织(例如胸腺、脾)或白细胞中表达荧光报告基因的转基因同源克隆；通过利用转基因技术在体内通过RNA干扰来揭示免疫相关基因的功能；通过产生识别免疫相关分子的新的莱维氏X.laevis特异性抗体(Abs)。 相关性：这一更新申请的总体目标是保护和促进非洲爪蛙作为生物医学研究，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生物医学研究资源设施，以造福整个科学界。