Abstract

The primary goal of the proposed research is to understand the molecular genetic basis of the development of B-cell lymphomas in mice. The identification of new loci that are implicated in causing murine B Our specific aims are: 1) identify the nature of alterations of the genes caused by the retroviral integrations at Evi-3, 2) show that the normal cellular roles of genes at Evi-3 are consistent with their roles as proto-oncogenes when altered by the retroviral integrations, 3) identify the role of EVI3 in human disease, and 4) obtain additional B-cell lymphomas from the AKXD mice for protein and RNA studies, B-cell differentiation studies, and additional molecular tagging studies. We plan to use molecular and cellular approaches to study gene function. These approaches include additional cloning, sequencing, and gene expression analysis. We also propose to develop additional resources for studying Evi-3 and for cloning new genes associated with other common sites of retroviral integration by aging mice from the AKXD recombinant inbred strains, and preserving tumor cells for expansion. These tumors will be valuable resources for our lab, as well as for other labs studying hematopoietic tumors or B-cell development.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29CA063229-04
Application #
2008486
Study Section
Pathology B Study Section (PTHB)
Project Start
1995-01-01
Project End
1999-12-31
Budget Start
1997-01-01
Budget End
1997-12-31
Support Year
4
Fiscal Year
1997
Total Cost
Indirect Cost

  Institution

Name
Lockheed Martin Energy Research Corp
Department
Type
DUNS #
City
Oak Ridge
State
TN
Country
United States
Zip Code
37831

  Publications

Hansen, G M; Skapura, D; Justice, M J (2000) Genetic profile of insertion mutations in mouse leukemias and lymphomas. Genome Res 10:237-43
Hansen, G M; Justice, M J (1999) Activation of Hex and mEg5 by retroviral insertion may contribute to mouse B-cell leukemia. Oncogene 18:6531-9
Hansen, G M; Tackles, D; Schwartz, C et al. (1999) A mouse chromosome 19 genetic map including the Lvis1 viral insertion site. Genomics 56:228-31
Hansen, G M; Justice, M J (1998) Pten, a candidate tumor suppressor gene, maps to mouse chromosome 19. Mamm Genome 9:88-90
Justice, M J; Stephenson, D A (1996) Encyclopedia of the mouse genome V. Mouse chromosome 13. Mamm Genome 6 Spec No:S232-44