The Research will entail an extensive series of studies on the 5' flanking regions of the light (NF_L) mid-sized (NF-M) and heavy (NF-H) neurofilament genes in order to identify the cis-acting elements and trans-acting factors that regulate the cell-specific expression of neurofilament genes. Promoter/enhancer elements of the NF genes will be fully sequenced. Defined DNA fragments, including deletion mutants, will be inserted into chimeric plasmids bearing the chloramphenicol transferase (CAT gene and the chimeric plasmids will be used to test the function of NF promoter/enhancer elements during transient transfections of neuronal and non-neuronal cell lines. Nuclear extracts from the same cell lines will be studied in footprinting and gel shift assays in order to map the common and unique binding sites along the 5' flanking regions of the NF genes. Correlation of binding sites with functional assays of the same elements in neuronal vs non-neuronal cells will be undertaken to identify the cis-acting elements and trans-acting factors that lead to specific expression of each NF gene.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08NS001451-03
Application #
3084508
Study Section
NST-2 Subcommittee (NST)
Project Start
1991-07-01
Project End
1994-06-30
Budget Start
1993-07-01
Budget End
1994-06-30
Support Year
3
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Schwartz, M L; Shneidman, P S; Bruce, J et al. (1994) Stabilization of neurofilament transcripts during postnatal development. Brain Res Mol Brain Res 27:215-20