Gabrb3 gene deficient mice: A potential model of autism spectrum disorder

Human chromosome 15q11-13 is associated with the neurodevelopmental disorders autism spectrum disorder, Angelman syndrome, and Prader-Willi syndrome. A number of genes have been identified within this region including a cluster of gamma-amino butyric acid type A receptor subunit genes, GABRB3, GABRA5, and GABRG3 (encoding the beta(3), alpha(5), and gamma(3) subunits, respectively). Numerous studies have demonstrated the importance of the GABAergic system in neurodevelopment; therefore the presence of a group of GABA(A) receptor genes within the locus is intriguing. The beta(3) subunit is widely expressed during the late embryonic to early postnatal period of brain development. A deficiently in the beta(3) subunit during this critical period would be expected to negatively impact the temporal ordering of neurogenesis and synaptogenesis. This would have subsequent ramifications in the maturation of circuts involved in supporting complex behaviours, motors skills, and cognition. As expected, mice deficient in the gabrb3 gene exhibit a wide assortment of neurochemical, electrophysiological, and behavioral abnormalities, many overlapping with traits typically observed in autism spectrum disorder and Angelman syndrome. These findings suggest a potential involvement of the GABRB3 gene in the etiology of these neurodevelopmental disorders. The gabrb3 gene deficient mouse has proved to be a valuable model in the critical examination of the interconnection between development, pathology, and behaviour as they relate to disorders of neurodevelopment.