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ARHGEF10 Knockout Mice Exhibit Autism‐Like Behavior and Altered Pain Sensation
Author(s) -
Lu DaiHua,
Liou HoungChi,
Liao HsiaoMei,
Chen ChiaHsiang,
Gau Susan ShurFen,
Fu WenMei
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.812.12
Subject(s) - autism , knockout mouse , autism spectrum disorder , rhoa , guanine nucleotide exchange factor , neuroscience , haploinsufficiency , psychology , gene knockout , neurodevelopmental disorder , genetics , biology , psychiatry , gene , gtpase , phenotype , signal transduction
Autism spectrum disorder (ASD) is a complex neurodevelopment disorder which can cause social, communication and development problems. Genetics certainly play a crucial role in ASD, however, how these different genes affect autistic‐like behavior is still unknown. Our previous CNV study discovered several novel CNVs associated ASD. Among the deleted CNV regions, a missense mutation of the ARHGEF10 is found to be the contributory factor in central nervous system diseases. Here we identified a new autism‐related gene, ARHGEF10, that codes a Rho guanine exchange factor 10 which is a member of guanine nucleotide exchange factor (GEF) family and activates small GTPases but preferentially for RhoA. To follow these CNV findings and gain deep insight into the pathogenesis of autism, we generated a ARHGEF10 knockout mice based on the identification of the patient with 8p23 terminal deletion. We found that the mice lacking ARHGEF10 displayed hyper‐locomotor activity in open field and alternated anxiety behavior in plus maze test. In addition, ARHGEF10 knockout mice showed impaired social interaction and social recognition in three‐chamber test. Moreover, the response to plantar and formalin test was reduced in ARHGEF10 knockout mice. However, knockout ARHGEF10 did not affect spatial learning memory and sensory motor gating. Our findings demonstrate that ARHGEF10 knockout mice displayed key symptoms of autism spectrum condition in human including decreased social interaction and increase spontaneous activities, reduced pain sensation. These results, together with the finding of CNVs in ASD patient, demonstrated that ARHGEF10 may be a candidate gene of autism. Support or Funding Information This work was supported by the Ministry of Science and Technology grants, 105‐2321‐B‐002‐020, Taiwan.