Very few neuronal cell lines exhibit differentiated properties of mature neurons. Most existing lines are immature and neuroblast-like, which limits their usefulness. Often the identity of the parental cell type from which the lines arose is unknown. We propose to derive cultured cell lines of catecholaminergic neurons or adrenal medullary cells from tissues of transgenic (TG) mice in which oncogenes are expressed from the rat tyrosine hydroxylase (TH) promoter. Initially we will determine which regulatory elements are necessary for cell specific expression of tyrosine hydroxylase in transgenic mice using both oncogene and non-oncogene reporter genes. We are particularly interested in determining if different TH expressing cells (CNS vs PNS or dopaminergic vs noradrenergic CNS neurons) require different enhancer elements. Transgenic animals will be generated with the appropriate TH enhancer-oncogene constructs and catecholaminergic tissues from oncogene-expressing animals will be cultured. Cell lines will be selected and characterized for a variety of neuronal specific traits. If necessary animals bearing several different oncogenes will be breed to increase the efficiency of immortalization. Lastly, TH+ cells will be ablated during development by targeting the expression of the diphtheria toxin gene or the Herpes simplex virus thymidine kinase gene to catecholaminergic cells in transgenic mice.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS029679-03
Application #
3416544
Study Section
Neurology C Study Section (NEUC)
Project Start
1991-07-20
Project End
1995-06-30
Budget Start
1993-07-01
Budget End
1994-06-30
Support Year
3
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Tufts University
Department
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02111