PT  - JOURNAL ARTICLE
AU  - Robert P. Carson
AU  - David Robertson
TI  - Genetic Manipulation of Noradrenergic Neurons
AID  - 10.1124/jpet.301.2.410
DP  - 2002 May 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 410--417
VI  - 301
IP  - 2
4099  - http://jpet.aspetjournals.org/content/301/2/410.short
4100  - http://jpet.aspetjournals.org/content/301/2/410.full
SO  - J Pharmacol Exp Ther2002 May 01; 301
AB  - The neurotransmitter norepinephrine has been the focus of intense investigation for nearly a century. With advances in technology come novel approaches for testing hypotheses about the physiological roles of norepinephrine and the genes involved in norepinephrine (NE) biosynthesis, metabolism, and noradrenergic signaling. Homologous recombination techniques, which generate mice deficient in specific gene products, aid the integrated physiologist and pharmacologist in the evaluation of protein function. Mouse models lacking proteins involved in NE biosynthesis or metabolism provide tools to expand the knowledge previously gleaned from pharmacologic studies. Removal of the biosynthetic enzymes tyrosine hydroxylase and dopamine-β-hydroxylase yield animals deficient in norepinephrine and have been used to further examine the role of NE in diverse physiologic roles. Complete removal of the vesicular monoamine transporter has demonstrated that mobilizing neurotransmitters to vesicles is required for animal survival. Lastly, the generation of animals in which the ability to remove NE from the synapse is impaired (norepinephrine transporter deficiency and extraneuronal monoamine transporter deficiency) and in which the enzymes responsible for the metabolism of NE have been removed (catechol-O-methyltransferase and monoamine oxidase) has facilitated the study of the long-term physiological consequences of altered NE homeostasis. The American Society for Pharmacology and Experimental Therapeutics