Programmed cell death (PCD) is a differentiative process that is required for the selective loss of cells during development. The predominant mechanism used for PCD in vertebrates is apoptosis, which is characterized by DNA degradation, chromatin margination along the nuclear envelope and membrane blebbing. While much is known about the triggers which initiate apoptosis, there is little information about the molecular mechanisms which mediate the process. This proposal takes advantage of a transgenic mouse where the majority of the T cells express the same T cell receptor. When this receptor is stimulated by the appropriate antigen in vivo, massive synchronized apoptotic cell death is induced in the T cells. Using these naturally dying thymocytes, we have generated a cDNA library. The library was screened by a plus/minus hybridization protocol, allowing us to isolate several putative cell death genes. It is proposed that cell death recombinants, which will be sequenced, expressed and used to generate antibodies which can aid in the analysis of the putative protein product.Experiments also are presented to examine how the expression of these genes are regulated during cell death in both T cells and non-immune cells.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
1R01GM047922-01A2
Application #
2185348
Study Section
Immunobiology Study Section (IMB)
Project Start
1992-09-30
Project End
1997-12-31
Budget Start
1994-01-01
Budget End
1994-12-31
Support Year
1
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of Massachusetts Amherst
Department
Veterinary Sciences
Type
Schools of Earth Sciences/Natur
DUNS #
153223151
City
Amherst
State
MA
Country
United States
Zip Code
01003
Smith, S W; McLaughlin, K A; Osborne, B A (1995) Molecular events in thymocyte apoptosis. Curr Top Microbiol Immunol 200:147-62