Lack of oligophrenin-1 expression has been implicated in non-specific X-linked mental retardation (MRX). Oligophrenin-1 is highly expressed in the brain, and contains a putative Rho GTPase activating protein (GAP) domain. The goal of this study is to determine how a lack of oligophrenin-1 results in a phenotype of mental retardation on a molecular and morphological level, and how its interaction(s) with Rho family GTPases contributes to this phenotype.
The specific aims are as follows: 1) To determine which GTPase oligophrenin-1 acts upon in a cellular context using Rhotekin Rho-Binding Domain and PAK3-binding assays to quantitate the amount of activated Rho GTPases in PC12 cells transfected with an oligophrenin-1 expression construct compared to control cells, 2) To determine what effect oligophrenin-1 has on cellular morphology in developing neurons by doing live cell imaging of biolistically-transfected pyramidal cells in hippocampal slices over time using two-photon microscopy, and 3) To determine how a lack of oligophrenin-1 affects dendritic length and spine formation in the above system. Information gained from studies on oligophrenin-1 will correlate basic cellular and molecular biology with the disease phenotype of mental retardation and will provide us with a better understanding of neuronal development and MRX. Ultimately, knowledge of these regulatory pathways may lead to treatment for this common condition.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31NS042062-02
Application #
6540506
Study Section
Special Emphasis Panel (ZRG1-MDCN-7 (01))
Program Officer
Nichols, Paul L
Project Start
2002-05-01
Project End
Budget Start
2002-05-01
Budget End
2003-04-30
Support Year
2
Fiscal Year
2002
Total Cost
$24,766
Indirect Cost
Name
Cold Spring Harbor Laboratory
Department
Type
DUNS #
065968786
City
Cold Spring Harbor
State
NY
Country
United States
Zip Code
11724