Abstract

We propose the following areas of investigation: 1. To study the determinants that regulate the transcription of the tissue plasminogen activator (t-PA) gene using three experimental murine systems: a) teratocarcinoma stem cells in various stages of differentiation; b) extracts of tissues that variably express the t-PA gene; and c) growing oocytes. 2. To investigate the role of t-PA in mouse embryonic development and normal physiology by: a) examining spatial and temporal aspects of t-PA mRNA expression in the embryo and adult by in situ analysis; b) in conjunction with Aim 1, determining which regions of the t-PA promoter are instrumental in tissue-specific expression by analyzing transgenic mice containing t-PA promoter/reporter gene constructs; and C) investigating the consequences of disruption of one or both copies of the t-PA gene in mice using the techniques of homologous recombination. 3. To characterize a new type of plasminogen activator (PA) produced by a Saturnidae moth caterpillar.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
2R01HD017875-08
Application #
3314890
Study Section
Mammalian Genetics Study Section (MGN)
Project Start
1991-02-01
Project End
1995-01-31
Budget Start
1991-02-01
Budget End
1992-01-31
Support Year
8
Fiscal Year
1991
Total Cost
Indirect Cost

  Institution

Name
State University New York Stony Brook
Department
Type
Schools of Medicine
DUNS #
804878247
City
Stony Brook
State
NY
Country
United States
Zip Code
11794

  Publications

Wells, J M; Strickland, S (1997) Regulated localization confers multiple functions on the protease urokinase plasminogen activator. J Cell Physiol 171:217-25
Carroll, P M; Tsirka, S E; Richards, W G et al. (1994) The mouse tissue plasminogen activator gene 5' flanking region directs appropriate expression in development and a seizure-enhanced response in the CNS. Development 120:3173-83
Wells, J M; Strickland, S (1994) Aprotinin, a Kunitz-type protease inhibitor, stimulates skeletal muscle differentiation. Development 120:3639-47
Carroll, P M; Richards, W G; Darrow, A L et al. (1993) Preimplantation mouse embryos express a cell surface receptor for tissue-plasminogen activator. Development 119:191-8
Huarte, J; Stutz, A; O'Connell, M L et al. (1992) Transient translational silencing by reversible mRNA deadenylation. Cell 69:1021-30
Salles, F J; Darrow, A L; O'Connell, M L et al. (1992) Isolation of novel murine maternal mRNAs regulated by cytoplasmic polyadenylation. Genes Dev 6:1202-12
Andrade-Gordon, P; Wang, S Y; Strickland, S (1992) Heparin-like activity in porcine follicular fluid and rat granulosa cells. Thromb Res 66:475-87
Salles, F J; Schechter, N; Strickland, S (1990) A plasminogen activator is induced during goldfish optic nerve regeneration. EMBO J 9:2471-7
Andrade-Gordon, P; Strickland, S (1990) Fractionation of heparin by chromatography on a tissue plasminogen activator-Sepharose column. Proc Natl Acad Sci U S A 87:1865-9
Vassalli, J D; Huarte, J; Belin, D et al. (1989) Regulated polyadenylation controls mRNA translation during meiotic maturation of mouse oocytes. Genes Dev 3:2163-71

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