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.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
DeLorey
Timothy M
TM
Molecular Research Institute, 1000 Elwell Court, Suite 105, Palo Alto, CA 94303, USA. tim@molres.org
Sahbaie
Peyman
P
Hashemi
Ezzat
E
Homanics
Gregg E
GE
Clark
J David
JD
D000704:Analysis of Variance; D000818:Animals; D001288:Attention / Q000502:physiology*; D001321:Autistic Disorder / Q000235:genetics / Q000503:physiopathology*; D002525:Cerebellar Cortex / Q000473:pathology*; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009425:Nesting Behavior / Q000502:physiology; D009929:Organ Size; D011963:Receptors, GABA-A / Q000235:genetics / Q000502:physiology*; D012919:Social Behavior
C546270:Gabrb3 protein, mouse; D011963:Receptors, GABA-A