Screening of functional norepinephrine transporter insensitive to cocaine inhibition and generation of knock-in mouse.
Year: 2009
Type: article
Abstract: This dissertation consists of three parts.The first part explores the possibility of screening a functional but cocaine insensitive norepinephrine transporter and generation of a cocaine insensitive knock-in mouse line, the second part attempts to identify residues in mouse norepinephrine transporter (NET) transmembrane domain 3 (TMD3) that would differentiate norepinephrine and dopamine uptake, while the third part discusses that two extracellular cysteines in dopamine transporter form a disulfide bond, which is vital for the transporter's function.Cocaine blocks dopamine transporter (DAT), NET and serotonin transporters (SERT) in the brain and increases extracellular neurotransmitter concentration in various brain regions.It is not known how each of these contributes to complex cocaine addictive effects.Genetically modified mice with a single one of these transporter removed still prefer cocaine, suggesting that none of them is absolutely required for cocaine rewarding effect.We have generated one unique knock-in mouse line, carrying a cocaine insensitive DAT.This mouse line does not show cocaine preference when given cocaine, which showed that DAT is necessary for cocaine rewarding effects.However, how NET is involved in cocaine addictive effect is still unknown.Based on the previous study, I performed several round of random mutagenesis around Hill, Brian O'Neill, Brad Martin and Bart Naughton for their great helpfulness and friendship.Working with them made my research in the lab rather enjoyable.
Author: Hua Wei
Institution: The Ohio State University
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W78628305