Gabrb3 gene deficient mice exhibit impaired social and exploratory behaviors, deficits in non-selective attention and hypoplasia of cerebellar vermal lobules: A potential model of autism spectrum disorder

GABA A receptors play an important regulatory role in the developmental events leading to the formation of complex neuronal networks and to the behaviors they govern. The primary aim of this study was to assess whether gabrb3 gene deficient (gabrb3 −/−) mice exhibit abnormal social behavior, a core...

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Bibliographic Details
Published in:Behavioural brain research 2008-03, Vol.187 (2), p.207-220
Main Authors: DeLorey, Timothy M., Sahbaie, Peyman, Hashemi, Ezzat, Homanics, Gregg E., Clark, J. David
Format: Article
Language:English
Subjects:
Analysis of Variance
Animals
Attention - physiology
Autistic Disorder - genetics
Autistic Disorder - physiopathology
Behavioral psychophysiology
Biological and medical sciences
Cerebellar Cortex - pathology
Cerebellar vermis
Child clinical studies
Developmental disorders
Disease Models, Animal
Exploration
Exploratory Behavior - physiology
Fundamental and applied biological sciences. Psychology
Infantile autism
Male
Medical sciences
Mice
Mice, Inbred C57BL
Mice, Knockout
Nest building
Nesting Behavior - physiology
Non-selective attention
Organ Size
Psychology. Psychoanalysis. Psychiatry
Psychology. Psychophysiology
Psychopathology. Psychiatry
Receptors, GABA-A - genetics
Receptors, GABA-A - physiology
Social Behavior
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Summary:GABA A receptors play an important regulatory role in the developmental events leading to the formation of complex neuronal networks and to the behaviors they govern. The primary aim of this study was to assess whether gabrb3 gene deficient (gabrb3 −/−) mice exhibit abnormal social behavior, a core deficit associated with autism spectrum disorder. Social and exploratory behaviors along with non-selective attention were assessed in gabrb3 −/−, littermates (gabrb3 +/+) and progenitor strains, C57BL/6J and 129/SvJ. In addition, semi-quantitative assessments of the size of cerebellar vermal lobules were performed on gabrb3 +/+ and gabrb3 −/− mice. Relative to controls, gabrb3 −/− mice exhibited significant deficits in activities related to social behavior including sociability, social novelty and nesting. In addition, gabrb3 −/− mice also exhibited differences in exploratory behavior compared to controls, as well as reductions in the frequency and duration of rearing episodes, suggested as being an index of non-selective attention. Gabrb3 −/− mice also displayed significant hypoplasia of the cerebellar vermis compared to gabrb3 +/+ mice. The observed behavioral deficits, especially regarding social behaviors, strengthens the face validity of the gabrb3 gene deficient mouse as being a model of autism spectrum disorder.
ISSN:0166-4328
1872-7549
DOI:10.1016/j.bbr.2007.09.009