Cloning and studying of the norepinephrine transporter.
This invention is the first cDNA clone encoding a norepinephrine transporter.
The cDNA allows high-level expression of the transporter in non-neuronal
eukaryotic and prokaryotic systems suitable for isolation of the protein. This
invention has applications in the research and drug development regarding
behavioral disorders and makes it possible to perform high-level structure
analysis of norepinephrine uptake. This will allow for a precise study of the
manner by which anti-depressants, cocaine, and amphetamine interact with the
transporter. Mutagenesis of the transporter is possible for analysis of residues
important for binding drugs and norepinephrine uptake and regulation. The cDNA
or parts of the molecule, in normal or mutated form, could also be transferred
into the germ line of transgenic animals to establish animal models for
disorders relating to norepinephrine uptake, secretion, or metabolism. Given the
wide spectrum of disorders for which norepinephrine-specific anti-depressants
are now prescribed, including obsessive-compulsive disorder, depression, as well
as eating, sleeping and panic disorders, such animal models might have a
profound influence on the design of therapeutic strategies.