Objetivo We propose to contribute to the mouse genome analysis by mapping the presently unknown genes involved in the control of two complex phenomena: Iymphocyte activation, and susceptibility to radiationinduced leukemia (RIL). These plans complement closely the aims of the principal project, where genes involved in development of different forms of cancer (lymphomas, tumors of colon, lung, and small intestine), atherosclerosis, and models of numerous human genetic diseases are being mapped and analyzed, and technologies and strategies are being developed to attack these tasks succesfully. In this associated project, two specific phenomena which lie within the field of interest and expertise of the participants are being studied using the technologies and approaches developed in the main project. The tasks of this additional project have, besides the contribution for genome analysis, a regional relevance for Central Europe, as the extant environmental contamination impairs the immune reactivity of large segments of the population, and there is an increased danger of radiation exposure. Until now, identification of the genes controlling complex phenomena has been very difficult, because several loci on different chromosomes are involved. Therefore, we will use the novel genetic tool, Recombinant Congenic Strains (RCS). A series of RCS contains appr. 20 homozygous strains, each of which contains a random small fraction of genome from a common donor inbred strain, and the majority of genes from a common background inbred strain. The individual donor strain's genes involved in the multigenic control of the studied trait are present in different RC strains, where they can be mapped and analyzed one by one. This proposal is based on extensive studies by both participants. Differences between RCS parental strains in a number of aspects of lymphocyte activation were identified and in RCS large differences in T lymphocyte proliferative response to IL-2, anti-CD3 antibody, as well as allogeneic lymphocytes were found. The RCS responded in a distinct pattern to these stimuli, indicating that each response is controlled by different genes. Also, susceptibility to RIL was tested and the susceptible and resistant RCS were identified. These studies substantiated the proposed approach and identified the RC strains suitable for mapping of the genes involved. In this project we will map the genes for the different pathways of Iymphocyte activation and the major susceptibility genes for the RIL with a precision of 0.5 cM, which will allow the search for their human homologues. Functional aspects of the genetic effect on Iymphocyte stimulation will be studied in order to obtain insight into the nature of the studied genes. The effects of RlL-susceptibility genes on the histological type and presence of activated oncogenes will be tested. Programa(s) IC-PECO/COPERNICUS - Scientific and technological cooperation between the European Community and European non-member countries, 1992- Tema(s) 0401 - CEEC participation in HUMAN CAPITAL & MOBILITY programme (NETWORKS) Convocatoria de propuestas Data not available Régimen de financiación CSC - Cost-sharing contracts Coordinador THE NETHERLANDS CANCER INSTITUTE / ANTONI VAN LEEUWENHOEK HOSPITAL Aportación de la UE Sin datos Dirección 121,Plesmanlaan 121 1066 CX AMSTERDAM Países Bajos Ver en el mapa Coste total Sin datos Participantes (2) Ordenar alfabéticamente Ordenar por aportación de la UE Ampliar todo Contraer todo Prague Institute of Advanced Studies Chequia Aportación de la UE Sin datos Dirección 2,Flemingovo nam 166 37 Praha Ver en el mapa Coste total Sin datos The Maria Sklodowska Curie Memorial Cancer Center and Institute of Oncology Polonia Aportación de la UE Sin datos Dirección 15,Wawelska 00 973 Warszawa Ver en el mapa Coste total Sin datos
