Transgenic mice expressing the PS1-A246E mutation: effects on spatial learning, exploration, anxiety, and motor coordination.
The functional consequence of the PS1-A246E mutation was assessed in transgenic mice on a background lacking the endogenous PS1 gene. These mice have elevated concentrations of A-beta protein (Abeta(42)) in the absence of plaque formation. By comparison to a mixed background strain (50% B6, 25% SJl, 25% 129Sv) controlled for age and gender, PS1-A246E transgenic mice displayed disinhibitory tendencies, as indicated by increased entries and duration in the open arms of the elevated plus-maze. Despite normal spontaneous alternation rates in a T-maze, latencies before responding were higher in PS1-A246E transgenic mice than controls. Moreover, the PS1-A246E transgenic mice fell more often from two stationary beams, but not from the coat-hanger and the rotorod. By contrast, ambulation in an automated photocell chamber and in an open-field was not affected. Nor was acquisition of place learning in the Morris water maze task. These results indicate that elevated Abeta(42) levels were insufficient for causing spatial defects but caused disinhibition, psychomotor slowing, and loss of motor skills in this model of familial Alzheimer's disease.
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Université de Rouen, Faculté de Médecine et de Pharmacie, 22 bld Gambetta, INSERM EPI 9906, Bâtiment de Recherche, Salle 1D18, 76183 Rouen Cedex, France. robert.lalonde@umontreal.ca
Qian
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Strazielle
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D000544:Alzheimer Disease / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000235:genetics*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D001143:Arousal / Q000235:genetics* / Q000502:physiology; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D005106:Exploratory Behavior / Q000502:physiology*; D005260:Female; D006801:Humans; D018782:Maze Learning / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009048:Motor Skills / Q000502:physiology*; D009154:Mutation / Q000235:genetics*; D009433:Neural Inhibition / Q000235:genetics / Q000502:physiology; D009949:Orientation / Q000502:physiology*; D004856:Postural Balance / Q000502:physiology; D053764:Presenilin-1; D011930:Reaction Time / Q000235:genetics / Q000502:physiology
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D002868:Chromosomal Proteins, Non-Histone; D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1