The goal of this work is to understand the regulation of neurotransmitter transport and the relationship of transport to synaptic transmission and neurological diseases such as Parkinson's Disease and neurodegeneration. Previous work identified a novel gene in Drosophila (dtr) that is involved in neurotransmitter transport. This gene has been cloned in mouse and named Lrrc50. The goal of this research is to understand the function of this newly discovered gene called Lrrc50 in the mouse. To undertake these studies modern genetic methods are being used to engineer mice with regional specific mutations of the Lrrc50 gene in the brain and in the eye. Electrophysiological, anatomical and behavioral methods will be used to study the function of the Lrrc50 gene in the mouse carrying brain and eye specific mutations of the Lrrc50 gene. In previous work a mouse has been genetically engineered with a floxed Lrrc50 gene. By mating this floxed Lrrc50 mouse to mice expressing the Cre recombinase driven by a brain or eye specific promoter regional knock-outs of the Lrrc50 gene have been obtained. Transmitter recycling and transport is critical for normal synaptic transmission yet little is known about the molecules that regulate synaptic function. Diseases such as mental illness, Alzheimer's disease, learning disabilities and mental retardation are thought to be diseases of the synapse. The innovation of this proposal is based upon our discovery of a novel gene involved in transmitter transport and the use of modern genetics in mouse and Drosophila.

Public Health Relevance

Transmitter recycling and transport is critical for normal communication between nerve cells yet little is known about the molecules that regulate transmitter recycling and transport. Diseases such as mental illness, Alzheimer's disease, learning disabilities and mental retardation are thought to be diseases of the communication system between nerve cells or the synapse. The innovation of this proposal is based upon our discovery of a novel gene involved in transmitter transport and the use of modern genetic engineering.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21MH090442-02
Application #
8041090
Study Section
Neurotransporters, Receptors, and Calcium Signaling Study Section (NTRC)
Program Officer
Asanuma, Chiiko
Project Start
2010-03-10
Project End
2013-01-31
Budget Start
2011-02-01
Budget End
2013-01-31
Support Year
2
Fiscal Year
2011
Total Cost
$235,744
Indirect Cost
Name
Salk Institute for Biological Studies
Department
Type
DUNS #
078731668
City
La Jolla
State
CA
Country
United States
Zip Code
92037