The overall objective of this proposal addresses itself to the analysis of specific gene interactions between the host and viral genomes in differentiation. Recently, we have identified and characterized a recombinant inbred (RI) mouse strain designated BXH-2, which spontaneously expresses a B-tropic MuLV throughout life and has a high incidence of myeloid leukemia. The virus is not present in the germline and is maternally transmitted. Southern analysis using a highly specific ecotropic MuLV DNA-derived probe indicated that 25 independent BXH-2 tumors contained newly acquired tumor-specific proviruses and 11 of these tumors contain only a single detectable tumor-specific provirus. The BXH-2 strain was the only BXH-strain among twelve, generated by crossing two low leukemic strains (C57BL/6J x C3H/HeJ) to have a high incidence of leukemia, thus one is presented with a disease model and eleven genotypically distinct controls. In this respect we feel that BXH-2 mice represent an important new model system for study of both host and viral factors involved in myeloid leukemogenesis. Specifically utilizing BXH-RI mice we propose to: 1. Determine the host genetic factors that may influence maternal transmission, virus expression and tumor incidence; 2. To clone recombinant DNA methodology, the representative tumor-specific proviruses detected in BXH-2 tumors and to elucidate their biochemical and biological function(s); we will also clone the host DNA fragments containing integrated viral DNA sequences and determine if these sequences are integrated in a chromosomal domain, are transcribed in tumor tissues, and homologous to any previously identified viral oncogenes. 3. To determine if the BXH-2 B-ecotropic virus which induces myeloid leukemias in vivo can induce the transformation of hematopoietic cells in vitro.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA031102-06
Application #
3169474
Study Section
Experimental Virology Study Section (EVR)
Project Start
1981-07-01
Project End
1987-06-30
Budget Start
1986-07-01
Budget End
1987-06-30
Support Year
6
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Jackson Laboratory
Department
Type
DUNS #
042140483
City
Bar Harbor
State
ME
Country
United States
Zip Code
04609
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