Impaired social interaction is one of the essential features of autism spectrum disorder (ASD). Our previous copy number variation (CNV) study discovered a novel deleted region associated with ASD. One of the genes included in the deleted region isARHGEF10. A missense mutation ofARHGEF10has been reported to be one of the contributing factors in several diseases of the central nervous system. However, the relationship between the loss of ARHGEF10 and the clinical symptoms of ASD is unclear.
We generatedArhgef10knockout mice as a model of ASD and characterized the social behavior and the biochemical changes in the brains of the knockout mice.
Compared with their wild-type littermates, theArhgef10-depleted mice showed social interaction impairment, hyperactivity, and decreased depression-like and anxiety-like behavior. Behavioral measures of learning in the Morris water maze were not affected byArhgef10deficiency. Moreover, neurotransmitters including serotonin, norepinephrine, and dopamine were significantly increased in different brain regions of theArhgef10knockout mice. In addition, monoamine oxidase A (MAO-A) decreased in several brain regions.
These results suggest thatARHGEF10is a candidate risk gene for ASD and that theArhgef10knockout model could be a tool for studying the mechanisms of neurotransmission in ASD.
Animal studies were approved by the Institutional Animal Care and Use Committee of National Taiwan University (IACUC 20150023). Registered 1 August 2015.