title: Human phenotypes and animal knockout models of genetic autonomic disorders.
abstract: Norepinephrine (NE) is a crucial neurotransmitter involved in autonomic regulation of blood pressure. Dopamine beta-hydroxylase (DBH), the norepinephrine transporter (NET), and the vesicular monoamine transporter subtype 2 catalyze intracellular NE biosynthesis, NE reuptake from the synapse, and vesicular transport, respectively. Genetic disorders in humans have been identified that render DBH, and the NET dysfunctional and result in cardiovascular and neurological abnormalities. Vesicular monoamine transporter subtype 2 (VMAT2) activity protects against neurotoxins, and reduced VMAT2 expression is implicated in drug addiction. Further investigation of the consequences of these genetic abnormalities has been achieved by the construction of mice strains deficient in the genes encoding DBH, NET, and VMAT2.
authors.affiliation: Autonomic Dysfunction Center, Department of Clinical Pharmacology, Vanderbilt University School of Medicine, AA-3228 Medical Center North, 1161 21st Avenue South, Nashville, TN 37232, USA.
authors.forename: Phillip C
authors.initials: PC
authors.lastname: Usera
authors.forename: Simi
authors.initials: S
authors.lastname: Vincent
authors.forename: David
authors.initials: D
authors.lastname: Robertson
mesh_terms: D000818:Animals; D001342:Autonomic Nervous System Diseases / Q000235:genetics*; D004195:Disease Models, Animal; D004299:Dopamine beta-Hydroxylase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D026901:Membrane Transport Proteins; D051379:Mice; D018345:Mice, Knockout; D009479:Neuropeptides; D050484:Norepinephrine Plasma Membrane Transport Proteins; D010641:Phenotype; D027981:Symporters / Q000235:genetics / Q000378:metabolism; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins
chemical_list: D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009479:Neuropeptides; D050484:Norepinephrine Plasma Membrane Transport Proteins; C493452:SLC18A2 protein, human; C493227:SLC6A2 protein, human; C493453:Slc18a2 protein, mouse; C493228:Slc6a2 protein, mouse; D027981:Symporters; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins; D004299:Dopamine beta-Hydroxylase