BIOMAT Database Logo BIOMAT Database Logo

Norepinephrine transporter heterozygous knockout mice exhibit altered transport and behavior. 2013

H M Fentress, and R Klar, and J J Krueger, and T Sabb, and S N Redmon, and N M Wallace, and J K Shirey-Rice, and M K Hahn
Division of Genetic Medicine, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.

The norepinephrine (NE) transporter (NET) regulates synaptic NE availability for noradrenergic signaling in the brain and sympathetic nervous system. Although genetic variation leading to a loss of NET expression has been implicated in psychiatric and cardiovascular disorders, complete NET deficiency has not been found in people, limiting the utility of NET knockout mice as a model for genetically driven NET dysfunction. Here, we investigate NET expression in NET heterozygous knockout male mice (NET(+/-) ), demonstrating that they display an approximately 50% reduction in NET protein levels. Surprisingly, these mice display no significant deficit in NET activity assessed in hippocampal and cortical synaptosomes. We found that this compensation in NET activity was due to enhanced activity of surface-resident transporters, as opposed to surface recruitment of NET protein or compensation through other transport mechanisms, including serotonin, dopamine or organic cation transporters. We hypothesize that loss of NET protein in the NET(+/-) mouse establishes an activated state of existing surface NET proteins. The NET(+/-) mice exhibit increased anxiety in the open field and light-dark box and display deficits in reversal learning in the Morris water maze. These data suggest that recovery of near basal activity in NET(+/-) mice appears to be insufficient to limit anxiety responses or support cognitive performance that might involve noradrenergic neurotransmission. The NET(+/-) mice represent a unique model to study the loss and resultant compensatory changes in NET that may be relevant to behavior and physiology in human NET deficiency disorders.

UI MeSH Term Description Entries
D008297 Male Males
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D002463 Cell Membrane Permeability A quality of cell membranes which permits the passage of solvents and solutes into and out of cells. Permeability, Cell Membrane
D002540 Cerebral Cortex The thin layer of GRAY MATTER on the surface of the CEREBRAL HEMISPHERES that develops from the TELENCEPHALON and folds into gyri and sulci. It reaches its highest development in humans and is responsible for intellectual faculties and higher mental functions. Allocortex,Archipallium,Cortex Cerebri,Cortical Plate,Paleocortex,Periallocortex,Allocortices,Archipalliums,Cerebral Cortices,Cortex Cerebrus,Cortex, Cerebral,Cortical Plates,Paleocortices,Periallocortices,Plate, Cortical
D006624 Hippocampus A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation. Ammon Horn,Cornu Ammonis,Hippocampal Formation,Subiculum,Ammon's Horn,Hippocampus Proper,Ammons Horn,Formation, Hippocampal,Formations, Hippocampal,Hippocampal Formations,Hippocampus Propers,Horn, Ammon,Horn, Ammon's,Proper, Hippocampus,Propers, Hippocampus,Subiculums
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001007 Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with ANXIETY DISORDERS. Angst,Anxiousness,Hypervigilance,Nervousness,Social Anxiety,Anxieties, Social,Anxiety, Social,Social Anxieties
D013574 Synaptosomes Pinched-off nerve endings and their contents of vesicles and cytoplasm together with the attached subsynaptic area of the membrane of the post-synaptic cell. They are largely artificial structures produced by fractionation after selective centrifugation of nervous tissue homogenates. Synaptosome
D050483 Dopamine Plasma Membrane Transport Proteins Sodium chloride-dependent neurotransmitter symporters located primarily on the PLASMA MEMBRANE of dopaminergic neurons. They remove DOPAMINE from the EXTRACELLULAR SPACE by high affinity reuptake into PRESYNAPTIC TERMINALS and are the target of DOPAMINE UPTAKE INHIBITORS. Dopamine Plasma Membrane Transporter Proteins,Neurotransmitter Transport Proteins, Dopamine-Specific,Neurotransmitter Transporters, Dopamine-Specific,DAT Dopamine Transporter,DAT Dopamine Transporter Proteins,Dopamine Carriers,Dopamine Transporter,Dopamine Transporter Proteins,Dopamine Uptake Complex,SLC6A3 Protein,Solute Carrier Family 6 (Neurotransmitter Transporter), Member 3 Protein,Carriers, Dopamine,Dopamine Transporter, DAT,Dopamine-Specific Neurotransmitter Transporters,Neurotransmitter Transport Proteins, Dopamine Specific,Neurotransmitter Transporters, Dopamine Specific,Protein, SLC6A3,Transporter Proteins, Dopamine,Transporter, DAT Dopamine,Transporter, Dopamine,Transporters, Dopamine-Specific Neurotransmitter
D050484 Norepinephrine Plasma Membrane Transport Proteins Sodium chloride-dependent neurotransmitter symporters located primarily on the PLASMA MEMBRANE of noradrenergic neurons. They remove NOREPINEPHRINE from the EXTRACELLULAR SPACE by high affinity reuptake into PRESYNAPTIC TERMINALS. The norepinephrine transporter regulates signal amplitude and duration at noradrenergic synapses and is the target of ADRENERGIC UPTAKE INHIBITORS. Neurotransmitter Transporters, Noradrenaline-Specific,Norepinephrine Plasma Membrane Transporter Proteins,Norepinephrine Plasma Membrane Transporters,NET Protein, Neuronal,Noradrenaline Plasma Membrane Transport Proteins,Noradrenaline Transporter,Norepinephrine Transporter,Norepinephrine Transporter Protein,SLC6A2 Protein,Sodium-Dependent Noradrenaline Transporter,Solute Carrier Family 6 Member 2,Neuronal NET Protein,Neurotransmitter Transporters, Noradrenaline Specific,Noradrenaline Transporter, Sodium-Dependent,Noradrenaline-Specific Neurotransmitter Transporters,Sodium Dependent Noradrenaline Transporter,Transporter Protein, Norepinephrine,Transporter, Noradrenaline,Transporter, Norepinephrine,Transporters, Noradrenaline-Specific Neurotransmitter

Related Publications

H M Fentress, and R Klar, and J J Krueger, and T Sabb, and S N Redmon, and N M Wallace, and J K Shirey-Rice, and M K Hahn
Altered reward circuitry in the norepinephrine transporter knockout mouse.
January 2013, PloS one,
H M Fentress, and R Klar, and J J Krueger, and T Sabb, and S N Redmon, and N M Wallace, and J K Shirey-Rice, and M K Hahn
Organic anion transporter 3 (Oat3/Slc22a8) knockout mice exhibit altered clearance and distribution of penicillin G.
October 2007, American journal of physiology. Renal physiology,
H M Fentress, and R Klar, and J J Krueger, and T Sabb, and S N Redmon, and N M Wallace, and J K Shirey-Rice, and M K Hahn
Cocaine-conditioned locomotion in dopamine transporter, norepinephrine transporter and 5-HT transporter knockout mice.
September 2009, Neuroscience,
H M Fentress, and R Klar, and J J Krueger, and T Sabb, and S N Redmon, and N M Wallace, and J K Shirey-Rice, and M K Hahn
JAZF1 heterozygous knockout mice show altered adipose development and metabolism.
August 2021, Cell & bioscience,
H M Fentress, and R Klar, and J J Krueger, and T Sabb, and S N Redmon, and N M Wallace, and J K Shirey-Rice, and M K Hahn
Altered response to antidepressant treatment in FoxG1 heterozygous knockout mice.
February 2010, Synapse (New York, N.Y.),
H M Fentress, and R Klar, and J J Krueger, and T Sabb, and S N Redmon, and N M Wallace, and J K Shirey-Rice, and M K Hahn
Heterozygous lipoprotein lipase knockout mice exhibit impaired hematopoietic stem/progenitor cell compartment.
December 2021, Animal models and experimental medicine,
H M Fentress, and R Klar, and J J Krueger, and T Sabb, and S N Redmon, and N M Wallace, and J K Shirey-Rice, and M K Hahn
Increased vulnerability to psychosocial stress in heterozygous serotonin transporter knockout mice.
January 2010, Disease models & mechanisms,
H M Fentress, and R Klar, and J J Krueger, and T Sabb, and S N Redmon, and N M Wallace, and J K Shirey-Rice, and M K Hahn
Metallothionein knockout and transgenic mice exhibit altered intestinal processing of zinc with uniform zinc-dependent zinc transporter-1 expression.
May 1998, The Journal of nutrition,
H M Fentress, and R Klar, and J J Krueger, and T Sabb, and S N Redmon, and N M Wallace, and J K Shirey-Rice, and M K Hahn
Altered visual function in monocarboxylate transporter 3 (Slc16a8) knockout mice.
August 2008, American journal of physiology. Cell physiology,
H M Fentress, and R Klar, and J J Krueger, and T Sabb, and S N Redmon, and N M Wallace, and J K Shirey-Rice, and M K Hahn
Altered behaviour, dopamine and norepinephrine regulation in stressed mice heterozygous in TPH2 gene.
June 2021, Progress in neuro-psychopharmacology & biological psychiatry,
Copied contents to your clipboard!