Alterations in the auditory startle response in Fmr1 targeted mutant mouse models of fragile X syndrome.
Fragile X syndrome results from inadequate production of the fragile X mental retardation protein (FMRP). Mice with a mutation targeted to the Fmr1 gene lack FMRP and thus are a valuable animal model for studying the behavioral and neural phenotype of this human disorder. Mice of two genetic backgrounds containing the Fmr1 mutation, C57BL/6J (C57-KO) and an F1 hybrid (C57BL/6J mutant x FVB/NJ; F1-KO) did not differ from control mice in behavior in the elevated plus maze or the open field. Both the C57-KO and F1-KO mice exhibited greater startle responses than normal mice to low intensity (80 dB) white noise bursts and decreased responses to high intensity (120 dB) white noise bursts. These behavioral alterations appear to be specific to the Fmr1 mutation since they are present on both genetic backgrounds. Furthermore, the mice lacking FMRP resemble individuals with fragile X syndrome in their increased sensitivity to low intensity auditory stimuli. These findings should prove useful in determining how the absence of FMRP alters the brain and behavior, and in testing potential treatments for fragile X syndrome.
Nielsen
Darci M
DM
Department of Pediatrics, C-233, University of Colorado School of Medicine, 4200 E. 9th Ave., Denver, CO 80262, USA. darci.nielsen@pharmacia.com
Derber
William J
WJ
McClellan
Danielle A
DA
Crnic
Linda S
LS
D000161:Acoustic Stimulation; D000818:Animals; D001007:Anxiety / Q000235:genetics / Q000503:physiopathology; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000502:physiology; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1; D005600:Fragile X Syndrome / Q000235:genetics* / Q000503:physiopathology*; D006185:Habituation, Psychophysiologic / Q000235:genetics; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics*; D016601:RNA-Binding Proteins; D013216:Reflex, Startle / Q000235:genetics*
D051860:Fragile X Messenger Ribonucleoprotein 1; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; C497684:Fmr1 protein, mouse