Heterozygous Disruption of Autism susceptibility candidate 2 Causes Impaired Emotional Control and Cognitive Memory
Mutations in the Autism susceptibility candidate 2 gene (AUTS2) have been associated with a broad range of psychiatric illnesses including autism spectrum disorders, intellectual disability and schizophrenia. We previously demonstrated that the cytoplasmic AUTS2 acts as an upstream factor for the Rh...
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Public Library of Science
2015
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4699902/ |
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pubmed-46999022016-01-14 Heterozygous Disruption of Autism susceptibility candidate 2 Causes Impaired Emotional Control and Cognitive Memory Hori, Kei Nagai, Taku Shan, Wei Sakamoto, Asami Abe, Manabu Yamazaki, Maya Sakimura, Kenji Yamada, Kiyofumi Hoshino, Mikio Research Article Mutations in the Autism susceptibility candidate 2 gene (AUTS2) have been associated with a broad range of psychiatric illnesses including autism spectrum disorders, intellectual disability and schizophrenia. We previously demonstrated that the cytoplasmic AUTS2 acts as an upstream factor for the Rho family small GTPase Rac1 and Cdc42 that regulate the cytoskeletal rearrangements in neural cells. Moreover, genetic ablation of the Auts2 gene in mice has resulted in defects in neuronal migration and neuritogenesis in the developing cerebral cortex caused by inactivation of Rac1-signaling pathway, suggesting that AUTS2 is required for neural development. In this study, we conducted a battery of behavioral analyses on Auts2 heterozygous mutant mice to examine the involvement of Auts2 in adult cognitive brain functions. Auts2-deficient mice displayed a decrease in exploratory behavior as well as lower anxiety-like behaviors in the absence of any motor dysfunction. Furthermore, the capability for novel object recognition and cued associative memory were impaired in Auts2 mutant mice. Social behavior and sensory motor gating functions were, however, normal in the mutant mice as assessed by the three-chamber test and prepulse inhibition test, respectively. Together, our findings indicate that AUTS2 is critical for the acquisition of neurocognitive function. Public Library of Science 2015-12-30 /pmc/articles/PMC4699902/ /pubmed/26717414 http://dx.doi.org/10.1371/journal.pone.0145979 Text en © 2015 Hori et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Hori, Kei Nagai, Taku Shan, Wei Sakamoto, Asami Abe, Manabu Yamazaki, Maya Sakimura, Kenji Yamada, Kiyofumi Hoshino, Mikio |
| spellingShingle |
Hori, Kei Nagai, Taku Shan, Wei Sakamoto, Asami Abe, Manabu Yamazaki, Maya Sakimura, Kenji Yamada, Kiyofumi Hoshino, Mikio Heterozygous Disruption of Autism susceptibility candidate 2 Causes Impaired Emotional Control and Cognitive Memory |
| author_facet |
Hori, Kei Nagai, Taku Shan, Wei Sakamoto, Asami Abe, Manabu Yamazaki, Maya Sakimura, Kenji Yamada, Kiyofumi Hoshino, Mikio |
| author_sort |
Hori, Kei |
| title |
Heterozygous Disruption of Autism susceptibility candidate 2 Causes Impaired Emotional Control and Cognitive Memory |
| title_short |
Heterozygous Disruption of Autism susceptibility candidate 2 Causes Impaired Emotional Control and Cognitive Memory |
| title_full |
Heterozygous Disruption of Autism susceptibility candidate 2 Causes Impaired Emotional Control and Cognitive Memory |
| title_fullStr |
Heterozygous Disruption of Autism susceptibility candidate 2 Causes Impaired Emotional Control and Cognitive Memory |
| title_full_unstemmed |
Heterozygous Disruption of Autism susceptibility candidate 2 Causes Impaired Emotional Control and Cognitive Memory |
| title_sort |
heterozygous disruption of autism susceptibility candidate 2 causes impaired emotional control and cognitive memory |
| description |
Mutations in the Autism susceptibility candidate 2 gene (AUTS2) have been associated with a broad range of psychiatric illnesses including autism spectrum disorders, intellectual disability and schizophrenia. We previously demonstrated that the cytoplasmic AUTS2 acts as an upstream factor for the Rho family small GTPase Rac1 and Cdc42 that regulate the cytoskeletal rearrangements in neural cells. Moreover, genetic ablation of the Auts2 gene in mice has resulted in defects in neuronal migration and neuritogenesis in the developing cerebral cortex caused by inactivation of Rac1-signaling pathway, suggesting that AUTS2 is required for neural development. In this study, we conducted a battery of behavioral analyses on Auts2 heterozygous mutant mice to examine the involvement of Auts2 in adult cognitive brain functions. Auts2-deficient mice displayed a decrease in exploratory behavior as well as lower anxiety-like behaviors in the absence of any motor dysfunction. Furthermore, the capability for novel object recognition and cued associative memory were impaired in Auts2 mutant mice. Social behavior and sensory motor gating functions were, however, normal in the mutant mice as assessed by the three-chamber test and prepulse inhibition test, respectively. Together, our findings indicate that AUTS2 is critical for the acquisition of neurocognitive function. |
| publisher |
Public Library of Science |
| publishDate |
2015 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4699902/ |
| _version_ |
1613519495848001536 |