The E2Fs are a family of transcription factors that interact with the protein product of the tumor suppressor gene Rb and thereby play a critical role as regulators of cell proliferation and differentiation. To study the function of two members of the E2F family, E2F-1 and E2F-2, we have begun to generate cells and mice that lack these genes using the technique of targeted disruption by homologous recombination. To achieve these overall goals we propose the following specific aims: (1) To generate cells that lack functional E2F-1 or E2F-2 by gene disruption in mouse embryonic stem (ES) cells. In preliminary experiments this has already been achieved for E2F-2, and the experiments are underway for E2F- 1; (2) To examine the growth and differentiation of ES cell lines that contain heterozygous or homozygous disruptions of the E2F-1 or E2F-2 genes, and compare the properties of these cells with wild-type ES cells; (3) To produce transgenic mice that are heterozygous or homozygous for the disrupted E2F-1 or E2F-2 genes by blastocyst injection of ES cells in which these genes have been disrupted; (4) To examine the phenotype of mice with disrupted E2F-1 or E2F-2 genes with respect to their embryonic development and adult phenotype with particular emphasis on the development and function of blood cell lineages. Taken together, the results of these experiments have the potential to give important new information regarding the specific functions of E2F-l and E2F-2 during cell proliferation, differentiation, and oncogenesis.

Project Start
1997-09-05
Project End
1998-08-31
Budget Start
1996-10-01
Budget End
1997-09-30
Support Year
4
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Children's Hospital Boston
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02115
Bauer, Daniel E; Orkin, Stuart H (2015) Hemoglobin switching's surprise: the versatile transcription factor BCL11A is a master repressor of fetal hemoglobin. Curr Opin Genet Dev 33:62-70
Kumar, Lalit; Chou, Janet; Yee, Christina S K et al. (2014) Leucine-rich repeat containing 8A (LRRC8A) is essential for T lymphocyte development and function. J Exp Med 211:929-42
Paik, Elizabeth J; Mahony, Shaun; White, Richard M et al. (2013) A Cdx4-Sall4 regulatory module controls the transition from mesoderm formation to embryonic hematopoiesis. Stem Cell Reports 1:425-36
Boatman, Sonja; Barrett, Francesca; Satishchandran, Sruthi et al. (2013) Assaying hematopoiesis using zebrafish. Blood Cells Mol Dis 51:271-6
Deshpande, Aniruddha J; Chen, Liying; Fazio, Maurizio et al. (2013) Leukemic transformation by the MLL-AF6 fusion oncogene requires the H3K79 methyltransferase Dot1l. Blood 121:2533-41
Jing, Lili; Durand, Ellen M; Ezzio, Catherine et al. (2012) In situ hybridization assay-based small molecule screening in zebrafish. Curr Protoc Chem Biol 4:
Kalaitzidis, Demetrios; Sykes, Stephen M; Wang, Zhu et al. (2012) mTOR complex 1 plays critical roles in hematopoiesis and Pten-loss-evoked leukemogenesis. Cell Stem Cell 11:429-39
Alexander, Matthew S; Kawahara, Genri; Kho, Alvin T et al. (2011) Isolation and transcriptome analysis of adult zebrafish cells enriched for skeletal muscle progenitors. Muscle Nerve 43:741-50
Baffour-Awuah, Nana Yaa; Delemarre, Eveline; Fujiwara, Yuko et al. (2011) Characterization of expression in mice of a transgene containing 3.3 kb of the human lactase-phlorizin hydrolase (LPH) 5' flanking sequence. Dig Dis Sci 56:59-69
Guyon, Jeffrey R; Mosley, Alycia N; Jun, Susan J et al. (2005) Delta-sarcoglycan is required for early zebrafish muscle organization. Exp Cell Res 304:105-15

Showing the most recent 10 out of 23 publications