Hyperactivity and novelty-induced hyperreactivity in mice lacking Rac3.
Rho family GTPases have been implicated as important regulators of neuronal development. Rac3 is a member of this family specifically expressed in vertebrate developing neurons, where it is coexpressed with the ubiquitous Rac1 GTPase. We have previously shown that Rac3 knockout mice are viable and fertile. The Rac3 protein shows highest expression around postnatal day 7 in brain regions relevant for cognitive behaviors. In this study we find that Rac3 knockout mice do not show defects in spatial reference memory assessed with water maze task, but they show a reduced behavioral flexibility to novel situations. Analysis of explorative behavior revealed hyperactive behavior and hyperreactivity to the presentation of new stimuli, as assessed by dark/light box, emergence and novel object tests. These defects were not due to reduced visual abilities, since visual acuity and contrast sensitivity were comparable in Rac3 knockout and wildtype littermates. Our data reinforce the notion that Rho family GTPases are important for normal cognitive development, and highlight specific functions of Rac3 that cannot be compensated by the coexpressed homologous Rac1.
Corbetta
Sara
S
Cell Adhesion Unit, Dibit, San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milano, Italy.
D'Adamo
Patrizia
P
Gualdoni
Sara
S
Braschi
Chiara
C
Berardi
Nicoletta
N
de Curtis
Ivan
I
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D000906:Antibodies / Q000494:pharmacology; D001522:Behavior, Animal / Q000502:physiology*; D015350:Contrast Sensitivity / Q000235:genetics; D005106:Exploratory Behavior / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D006948:Hyperkinesis / Q000235:genetics* / Q000503:physiopathology*; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D010775:Photic Stimulation / Q000379:methods; D013997:Time Factors; D014741:Video Recording / Q000379:methods; D014792:Visual Acuity / Q000235:genetics; D020744:rac GTP-Binding Proteins / Q000172:deficiency* / Q000276:immunology
D000906:Antibodies; C498771:Rac3 protein, mouse; D020744:rac GTP-Binding Proteins