Arid1b haploinsufficiency causes abnormal brain gene expression and autism-related behaviors in mice

Mihiro Shibutani, Takuro Horii, Hirotaka Shoji, Sumiyo Morita, Mika Kimura, Naomi Terawaki, Tsuyoshi Miyakawa, Izuho Hatada

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with core symptoms that include poor social communication, restricted interests, and repetitive behaviors. Several ASD mouse models exhibit impaired social interaction, anxiety-like behavior, and elevated perseveration. Large-scale whole exome sequencing studies identified many genes putatively associated with ASD. Like chromodomain helicase DNA binding protein 8 (CHD8), the most frequently mutated gene in individuals with ASD, the candidate gene AT-rich interaction domain 1B (ARID1B) encodes a chromatin remodeling factor. Arid1b heterozygous knockout (hKO) mice exhibited ASD-like traits related to social behavior, anxiety, and perseveration, in addition to associated features reported in some cases of ASD, such as reduced weight, impaired motor coordination, and hydrocephalus. Hydrocephalus was present in 5 of 91 hKO mice, while it was not observed in wild-type littermates (0 of 188). Genome-wide gene expression patterns in Arid1b hKO mice were similar to those in ASD patients and Chd8-haploinsufficient mice, an ASD model, and to developmental changes in gene expression in fast-spiking cells in the mouse brain. Our results suggest that Arid1b haploinsufficiency causes ASD-like phenotypes in mice.

Original languageEnglish
Article number1872
JournalInternational journal of molecular sciences
Volume18
Issue number9
DOIs
Publication statusPublished - 01-09-2017

Fingerprint

Haploinsufficiency
gene expression
Autistic Disorder
Gene expression
brain
mice
Brain
Genes
disorders
Gene Expression
causes
knockout mice
Knockout Mice
anxiety
genes
DNA-Binding Proteins
Hydrocephalus
Chromatin
DNA
Anxiety

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

Shibutani, Mihiro ; Horii, Takuro ; Shoji, Hirotaka ; Morita, Sumiyo ; Kimura, Mika ; Terawaki, Naomi ; Miyakawa, Tsuyoshi ; Hatada, Izuho. / Arid1b haploinsufficiency causes abnormal brain gene expression and autism-related behaviors in mice. In: International journal of molecular sciences. 2017 ; Vol. 18, No. 9.
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Arid1b haploinsufficiency causes abnormal brain gene expression and autism-related behaviors in mice. / Shibutani, Mihiro; Horii, Takuro; Shoji, Hirotaka; Morita, Sumiyo; Kimura, Mika; Terawaki, Naomi; Miyakawa, Tsuyoshi; Hatada, Izuho.

In: International journal of molecular sciences, Vol. 18, No. 9, 1872, 01.09.2017.

Research output: Contribution to journalArticle

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