The goal of this renewal application is to continue maintaining and developing the world's most comprehensive research resource specializing in the use of the amphibian Xenopus laevis for biomedical and immunological research. Interests and relevance of X. laevis for human health are due to the remarkable similarity of its immune system with that of human, the accessibility to experimentation at all developmental stages, as well as the availability of large genetic resources, invaluable MHC-defined inbred strains and clones of frogs and tools such as fibroblast and lymphoid tumor cell lines, monoclonal antibodies, MHC tetramers and batteries of validated PCR primers for immune-relevant genes. These animals and reagents need to be preserved, enriched, and made available to the scientific community. The broad objective of this renewal application is to continue managing, safeguarding, promoting and further developing X. laevis as a unique multi-faceted experimental platform for research in fundamental and medical immunology and for the benefit of the whole scientific community. As in previous proposals, 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 and reagents, not commercially available, upon request;by assisting, training, and informing scientists and students about X. laevis;and by promoting information, accessibility and public awareness of the resource through a frequently updated website connected with other important Xenopus resources in US and in the world as well as with sites involved with immunology, amphibian and conservation biology. (2) Development of new experimental animals, methodologies, and reagents by generating transgenic (Tg) X. laevis inbred lines and clones with RNA-mediated loss-of-function, new fluorescent Tg reporter inbred MHC-defined lines and clones, new reagents (monoclonal antibodies, MHC tetramers), and by developing X. laevis tadpoles for real time intravital microscopy using fluorescent ranavirus recombinants, tumor transfectants and X. laevis transgenic reporter lines to visualize antiviral and antitumor immune responses. In addition to maintaining a research platform that is crucial for the Xenopus scientific community, this project promotes the development of new approaches and technologies that can be rapidly and broadly applied for innovative insight into tissue and organ physiology, immunology and developmental biology. The development and application of these tools and technologies will contribute to the efforts of the Xenopus community assisted by the NIH to establish Xenopus as a relevant model for biomedical research. Given the high degree of genetic and functional similarities between Xenopus and mammalian immune and other physiological systems, it is anticipated that outcomes from research promoted by the X. laevis Research Resource will lead to applications relevant to human related research and therapy development.

Public Health Relevance

Public Health Relevance Statement 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 that includes animals, reagents, information and training opportunity for biomedical research for the benefit of the whole scientific community.

National Institute of Health (NIH)
Resource-Related Research Projects (R24)
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Special Emphasis Panel (ZAI1)
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Leitner, Wolfgang W
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University of Rochester
School of Medicine & Dentistry
United States
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Cheng, Kwang; Escalon, B Lynn; Robert, Jacques et al. (2014) Differential transcription of fathead minnow immune-related genes following infection with frog virus 3, an emerging pathogen of ectothermic vertebrates. Virology 456-457:77-86
Robert, Jacques; Edholm, Eva-Stina (2014) A prominent role for invariant T cells in the amphibian Xenopus laevis tadpoles. Immunogenetics 66:513-23
Grayfer, Leon; De Jesús Andino, Francisco; Robert, Jacques (2014) The amphibian (Xenopus laevis) type I interferon response to frog virus 3: new insight into ranavirus pathogenicity. J Virol 88:5766-77
Edholm, Eva-Stina; Goyos, Ana; Taran, Joseph et al. (2014) Unusual evolutionary conservation and further species-specific adaptations of a large family of nonclassical MHC class Ib genes across different degrees of genome ploidy in the amphibian subfamily Xenopodinae. Immunogenetics 66:411-26
Haynes-Gilmore, Nikesha; Banach, Maureen; Edholm, Eva-Stina et al. (2014) A critical role of non-classical MHC in tumor immune evasion in the amphibian Xenopus model. Carcinogenesis 35:1807-13
Sifkarovski, Jason; Grayfer, Leon; De Jesús Andino, Francisco et al. (2014) Negative effects of low dose atrazine exposure on the development of effective immunity to FV3 in Xenopus laevis. Dev Comp Immunol 47:52-8
Edholm, Eva-Stina; Grayfer, Leon; Robert, Jacques (2014) Evolution of nonclassical MHC-dependent invariant T cells. Cell Mol Life Sci 71:4763-80
Robert, Jacques; Grayfer, Leon; Edholm, Eva-Stina et al. (2014) Inflammation-induced reactivation of the ranavirus Frog Virus 3 in asymptomatic Xenopus laevis. PLoS One 9:e112904
Suurvali, Jaanus; Robert, Jacques; Boudinot, Pierre et al. (2013) R4 regulators of G protein signaling (RGS) identify an ancient MHC-linked synteny group. Immunogenetics 65:145-56
Nedelkovska, Hristina; Robert, Jacques (2013) Hsp72 mediates stronger antigen-dependent non-classical MHC class Ib anti-tumor responses than hsc73 in Xenopus laevis. Cancer Immun 13:4

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