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 stretchattend 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.

Somatosensory and sensorimotor consequences associated with the heterozygous disruption of the autism candidate gene, Gabrb3

“…We observed no gender difference in the number of marbles buried by male or female control mice as has also been reported elsewhere [26, 46]. Significant genotype differences in marble burying behavior was observed amongst female mouse variants (F 2,41 =4.86, p <0.05) with post hoc tests revealing female p−/m+ mice, but not p+/m− mice, to be significantly different from female controls ( p <0.01).…”

“…Previous studies utilizing the V1aR gene knockout mouse [13] and the Gabrb3 gene knockout mouse [26], both models of ASD, reported reductions in marble burying behavior. In the current study, male and female p−/m+ mice also displayed reduced marble burying behavior while their p+/m− counterparts did not (Table 1).…”

“…The above findings appear to be counterintuitive as one would have predicted that an autism model would exhibit more preservative behavior, not less, leading to an increase in marbles buried. We considered whether tactile hypersensitivity or hypotonia, both observed in Gabrb3 knockout mice [26, 65], might account for reduced digging in p−/m+ mice. However, no evidence for hypotonia, as assessed by the wire-hanging task, was observed in any heterozygote and no association between tactile hypersensitivity and the number of marble buried was apparent.…”

Force plate for measuring small animal forces by digital speckle pattern interferometry

“…In some diseases, the muscle strength is the parameter that characterizes the state of development of the illness and several tests have been developed for their knowledge. For this purpose, a variety of tests like rotarod test, hanging wire test, open field or walking pattern test [3][4][5] have been developed. However, these tests need the training of the animal and they have a certain grade of subjectivity.…”

Energy Homeostasis in children with Prader- Willi syndrome

“…GABA receptors are expressed in central nervous system, testes, heart, lungs, pancreas, intestine, kidneys and adrenal glands. Mice with GABA receptor β3 gene deficiency suffer from hypotonia and neuro-behavioural problems similar to PWS (Hashemi, Sahbaie et al 2007). Using [ higher plasma GABA level in PWS (Ebert, Schmidt et al 1997).…”