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Modelling human pre-leukemic syndrome in mice: functional dissection of the 5q31 candidate region

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

Funding Scheme

CSC - Cost-sharing contracts

Coordinator

FOUNDATION OF RESEARCH AND TECHNOLOGY - HELLAS
Address
Vassilika Vouton
71110 Iraklion
Greece

Participants (4)

HUMBOLDT-UNIVERSITAET BERLIN
Germany
Address
20-21,Schumanstrasse 20-21
10117 Berlin
INSTITUTE OF CANCER RESEARCH : ROYAL CANCER HOSPITAL
United Kingdom
Address
Old Brompton Road 123
SW7 3RP London
KLINIKUM DER FRIEDRICH-SCHILLER-UNIVERSITAET JENA
Germany
Address
Bachstrasse 18
07740 Jena
THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
United Kingdom
Address
Roosevelt Drive
OX3 7BN Oxford/headington