Disruption of the dopamine beta-hydroxylase gene in mice suggests roles for norepinephrine in motor function, learning, and memory.
Mice unable to synthesize norepinephrine (NE) were created by targeted disruption of the dopamine beta-hydroxylase (DBH) gene. DBH-deficient (DBH -/-) mice display normal home cage activity; however, they swim more slowly than their littermates, and some drown. The mutant mice also perform less well on a rapidly rotating rod, and approximately 20% do not learn to walk when the rod begins to turn. Restoration of NE with dihydroxyphenylserine eliminated these motor deficits. DBH -/- mice exhibit normal learning and retention of a passive avoidance paradigm; however, they do not master an active-avoidance paradigm as readily as controls and exhibit more rapid extinction of the active-avoidance task. DBH -/- mice learn to find the hidden platform in the Morris water maze in spite of their slower swim speed and show normal preference for the correct quadrant in the transfer test immediately after training. However, this preference declines relative to controls during the next 2 days.
Thomas
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Howard Hughes Medical Institute, Department of Biochemistry, University of Washington, Seattle 98195-7370, USA.
Palmiter
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D000818:Animals; D001362:Avoidance Learning / Q000502:physiology*; D001921:Brain / Q000502:physiology; D004299:Dopamine beta-Hydroxylase / Q000235:genetics*; D004924:Escape Reaction / Q000502:physiology*; D018782:Maze Learning / Q000502:physiology*; D011939:Mental Recall / Q000502:physiology*; D051379:Mice; D008818:Mice, Neurologic Mutants; D009043:Motor Activity / Q000502:physiology*; D009048:Motor Skills / Q000502:physiology*; D009638:Norepinephrine / Q000502:physiology*; D009949:Orientation / Q000502:physiology; D011340:Problem Solving / Q000502:physiology*; D012153:Retention, Psychology / Q000502:physiology; D014163:Transfer, Psychology
D004299:Dopamine beta-Hydroxylase; D009638:Norepinephrine