title: Gabrb3 gene deficient mice exhibit increased risk assessment behavior, hypotonia and expansion of the plexus of locus coeruleus dendrites.
abstract: Gabrb3 gene deficient (gabrb3(-/-)) mice, control littermates (gabrb3(+/+)) and their progenitor strains C57Bl/6J and 129/SvJ were assessed for changes in the morphology of the main noradrenergic nuclei, the locus coeruleus (LC) and LC-associated behaviors including anxiety and muscle tone. While the area defined by the cell bodies of the LC was found not to differ between gabrb3(-/-) mice and controls, the pericoerulear dendritic zone of the LC was found to be significantly enlarged in gabrb3(-/-) mice. Relative to controls, gabrb3(-/-) mice were also found to be hypotonic, as was indicated by poor performance on the wire hanging task. Gabrb3(-/-) mice also exhibited a significant increase in stretch-attend posturing, a form of risk assessment behavior associated with anxiety. However, in the plus maze, a commonly used behavioral test for assessing anxiety, no significant difference was observed between gabrb3(-/-) and control mice. Lastly, relative to controls, gabrb3(-/-) mice exhibited significantly less marble burying behavior, a method commonly used to assess obsessive-compulsive behavior. However, the poor marble burying performance of the gabrb3(-/-) mice could be associated with the hypotonic condition exhibited by these mice. In conclusion, the results of this study indicate that the gabrb3 gene contributes to LC noradrenergic dendrite development with the disruption of this gene in mice resulting in an enlarged plexus of LC dendrites with a concurrent reduction in muscle tone and marble burying behavior, an increase in risk assessment behavior but no change in the plus maze parameters that are commonly used for assessing anxiety.
authors.affiliation: Molecular Research Institute, Mountain View, CA 94043, USA.
authors.forename: Ezzat
authors.initials: E
authors.lastname: Hashemi
authors.forename: Peyman
authors.initials: P
authors.lastname: Sahbaie
authors.forename: M Frances
authors.initials: MF
authors.lastname: Davies
authors.forename: J David
authors.initials: JD
authors.lastname: Clark
authors.forename: Timothy M
authors.initials: TM
authors.lastname: DeLorey
mesh_terms: D000818:Animals; D001008:Anxiety Disorders / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D001522:Behavior, Animal / Q000502:physiology; D003712:Dendrites / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D008125:Locus Coeruleus / Q000002:abnormalities* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009123:Muscle Hypotonia / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D009421:Nervous System Malformations / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D009433:Neural Inhibition / Q000235:genetics; D011963:Receptors, GABA-A / Q000235:genetics*; D012309:Risk-Taking; D009435:Synaptic Transmission / Q000235:genetics; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: C546270:Gabrb3 protein, mouse; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid