REGULATION OF PERIPHERAL NERVE-SPECIFIC NA CHANNEL, PN1

Project: Research project

Project Details

Description

The long-term goal of this research is to understand the mechanisms that
regulate the temporal and tissue specific expression of the peripheral
nervous system specific Na channel, PN1. Na channels, expressed in the
axons and cell bodies of peripheral nervous system (PNS) neurons, are
in large part responsible for making these cells electrically excitable.
The PN1 Na channel has the following unique properties: first, it is one
of the only genes expressed predominantly in the PNS; and second, PN1
is rapidly and dramatically upregulated upon brief (1 min.) exposure to
nerve growth factor (NGF) and interferon gamma (IFNgamma) by an as yet
unknown mechanism. Our research plan is to: 1) Use genetic and
biochemical techniques to identify PN1 regulatory DNA elements that
confer the PN1 expression pattern on reporter genes transfected into
several cell lines. 2) Determine the mechanism-immediate early genes and
response elements-by which PN1 is upregulated by NGF and IFNgamma. The
yeast one hybrid screen developed In the Pls lab will be used to isolate
immediate early genes. 3) Test the constructs isolated in 1 and 2 for
their ability to drive expression of a reporter gene in vivo by creating
transgenic mice expressing the different constructs. Results from these
experiments should be applicable in an experimental or therapeutic
context to drive gene expression specifically PNS.
StatusFinished
Effective start/end date7/10/987/9/00

Funding

  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke

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