Objective The goal of this project is to develop novel expression systems and mutant transgenic organisms, in order to gain insights into the role of the 5q31 region, revealing the functions of genes involved in haematopoiesis and the leukaemia processes. To this end, we will model aspects of the pre-leukemic 5q- deletion-mutation syndrome in the mouse, by using a series of homologous recombination and novel expression systems strategies. More specifically, based on a previously successful technological approach, we plan to 1) delete in the mouse the synthetic candidate 'critical region' between the GM-CSF /IL3 and TCF1 genes, included in our constructed human YAC contig. Our approach will utilize the Cre-IoxP recombination system combined with conditional targeting, to induce the deletion of the 5q31 region in the adult mouse myeloid cells only (like in humans), by linking the Cre recombines gene, under the myeloid and adult-specific promoter of the myeloperoxidase gene. Thus, the generated animal models containing precise large chromosomal deletions, occurring as acquired somatic mutations, will accurately mimic the human pre-leukaemia syndrome 2) Systematically analyse the resulting phenotypes of the mice by differential display technology approaches, to reveal the deregulated pathways and gene networks occurring in these models Fields of science natural sciencesbiological sciencesgeneticsmutationmedical and health sciencesclinical medicineoncologyleukemia Programme(s) FP5-LIFE QUALITY - Specific Programme for research, technological development and demonstration on "Quality of life and management of living resources", 1998-2002 Topic(s) 1.1.1.-8. - Research into genomes and diseases of genetic origin Call for proposal Data not available Funding Scheme CSC - Cost-sharing contracts Coordinator FOUNDATION OF RESEARCH AND TECHNOLOGY - HELLAS EU contribution No data Address Vassilika Vouton 71110 IRAKLION Greece See on map Total cost No data Participants (4) Sort alphabetically Sort by EU Contribution Expand all Collapse all HUMBOLDT-UNIVERSITAET BERLIN Germany EU contribution No data Address 20-21,Schumanstrasse 20-21 10117 BERLIN See on map Total cost No data INSTITUTE OF CANCER RESEARCH : ROYAL CANCER HOSPITAL United Kingdom EU contribution No data Address Old Brompton Road 123 SW7 3RP LONDON See on map Total cost No data KLINIKUM DER FRIEDRICH-SCHILLER-UNIVERSITAET JENA Germany EU contribution No data Address Bachstrasse 18 07740 JENA See on map Total cost No data THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD United Kingdom EU contribution No data Address Roosevelt Drive OX3 7BN OXFORD/HEADINGTON See on map Total cost No data
