HUMAN AND MURINE DOPAMINE TRANSPORTER GENE ANALYSES AND DOPAMINERGIC DISORDERS

Project: Research project

Project Details

Description

The dopamine transporter/cocaine receptor (DAT) is the site at which
cocaine exerts rewarding/reinforcing effects as well as playing a central
role in termination of dopamine neurotransmission. Cloning of rat and
human DAT CDNAS by Addiction Research Center scientists during the
preceding FY provided primary sequence information and CDNA clones that
facilitated isolation of genomic clones from rodent and human,
development of polymorphic genetic markers, and application of these
markers to human disorders hypothesized to involve dopaminergic system
dysfunction or those treatable with dopaminergic agents.

Screening of phage and cosmid genomic libraries from human and murine
embryonic stem cells resulted in identification of several human and
murine genomic clones of more than 20 kb (murine) and more than 9 kb
(human), respectively. Attempts to drive expression of reporter genes
with several constructs including the murine "promoter/enhancer"
sequences were unrevealing, suggesting the possibility of strong cell-
type specificity in the transporter's expression.

Polymorphic genetic human transporter gene markers were used for analysis
individuals with Tourette's syndrome and Parkinson's disease. No linkage
between the DAT gene and Tourette's Syndrome was demonstrated in two
large and 10 small kindreds; 5 centimorgans on either side of the DAT
gene can be excluded by these analyses. No variation in the number of
copies of the VNTR passed between generations has been detected in these
families. No association between Parkinson's disease and DAT gene
markers can be identified.
StatusNot started

Funding

  • National Institute on Drug Abuse

Fingerprint Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.