Objetivo The proposed project is dedicated to the development of a novel approach, called FLPFLEX, to manipulate gene expression in the mouse, for dissecting complex genetic pathways and for providing more accurate models of human disease. By engaging the cell's ow n transcriptional regulatory circuits to capture novel expression patterns, FLPFLEX cassette exhange allows multiple rapid manipulations in a single genomic locus, providing powerful and adaptable tools for designing increasingly complex genetic models of human physiology and pathology. In Module 1 will include development of readout vector technologies and establishment of the FLPFLEX cell library. We will develop flexible genomic insertion cassettes carrying modifications to allow recombinase-mediated cas sette exchange of effector genes of interest. The FLPFLEX vector carrying a multifunctional tag will be randomly incorporated into the genome of embryonic stem (ES) cells. Since a majority of all mouse genes are expressed in ES cells, multiple ES clones ca rrying an expressed FLPFLEX tag can be readily selected. We will sequence and identify 10,000 FLPFLEX cassette integration sites using mouse genomic information. Predicted expression patterns of the captured gene locus will be verified by manual and automa ted in situ hybridization of adult tissues. In Module 2, we will select 50 FLPFLEX clones for further characterization and focused studies in vivo. We will introduce different effector genes via cassette exchange in selected FLPFLEX cell clones. Germ line transmission of these exchange cassettes in mice will yield novel patterns for conditional effector genes such as Cre recombinase, or allelic exchange of individual mutated cDNAs of disease genes. The project is strategically designed to provide an efficie nt mechanism for generating, characterising and disseminating these models. Information and reagents generated will be disseminated on a publicly accessible database. ' Ámbito científico natural sciencescomputer and information sciencesdatabasesmedical and health sciencesbasic medicinepathologymedical and health sciencesbasic medicinephysiologynatural sciencesbiological sciencesgeneticsgenomes Palabras clave Conditional alleles Gene Expression Human Disease Mouse models Programa(s) FP6-LIFESCIHEALTH - Life sciences, genomics and biotechnology for health: Thematic Priority 1 under the Focusing and Integrating Community Research programme 2002-2006. Tema(s) LSH-2003-1.1.0-1 - Topics for Specific Targeted Research Project in the area of Fundamental knowledge and basic tools for functional genomics in all organisms Convocatoria de propuestas FP6-2003-LIFESCIHEALTH-I Consulte otros proyectos de esta convocatoria Régimen de financiación STIP - Specific Targeted Innovation Project Coordinador EUROPEAN MOLECULAR BIOLOGY LABORATORY Aportación de la UE Sin datos Dirección Meyerhofstrasse 1 HEIDELBERG Alemania Ver en el mapa Enlaces Sitio web Opens in new window Coste total Sin datos Participantes (4) Ordenar alfabéticamente Ordenar por aportación de la UE Ampliar todo Contraer todo FONDAZIONE TELETHON Italia Aportación de la UE Sin datos Dirección VIA GUGLIELMO SALICETO, 5 ROME Ver en el mapa Enlaces Sitio web Opens in new window Coste total Sin datos GSF - NATIONAL RESEARCH CENTER FOR ENVIRONMENT AND HEALTH, GMBH Alemania Aportación de la UE Sin datos Dirección Ingolstaedter Landstrasse 1 NEUHERBERG Ver en el mapa Enlaces Sitio web Opens in new window Coste total Sin datos ISTITUTO DI RICERCHE DI BIOLOGIA MOLECOLARE P. ANGELETTI Italia Aportación de la UE Sin datos Dirección Via Pontina Km. 30,600 POMEZIA (RM) Ver en el mapa Coste total Sin datos HELMHOLTZ-ZENTRUM FÜR INFEKTIONSFORSCHUNG GMBH Alemania Aportación de la UE Sin datos Dirección Inhoffenstrasse 7 BRAUNSCHWEIG Ver en el mapa Enlaces Sitio web Opens in new window Coste total Sin datos
