Arid1b Haploinsufficiency Causes Abnormal Brain Gene Expression and Autism-Related Behaviors in Mice

International Journal of Molecular Sciences - Tập 18 Số 9 - Trang 1872
Mihiro Shibutani1, Takuro Horii1, Hirotaka Shoji2, Sumiyo Morita1, Mika Kimura1, Naomi Terawaki1, Tsuyoshi Miyakawa2, Izuho Hatada1
1Laboratory of Genome Science, Biosignal Genome Resource Center, Institute for Molecular and Cellular Regulation, Gunma University, 3-39-15 Showa-machi, Maebashi, Gunma 371-8512, Japan
2Division of Systems Medical Science, Institute for Comprehensive Medical Science, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi, 470-1192, Japan

Tóm tắt

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.

Từ khóa


Tài liệu tham khảo

Wing, 1981, Language, social, and cognitive impairments in autism and severe mental retardation, J. Autism Dev. Disord., 11, 31, 10.1007/BF01531339

Wing, 1979, Severe impairments of social interaction and associated abnormalities in children: Epidemiology and classification, J. Autismaal Dev. Disord., 9, 11, 10.1007/BF01531288

Turner, 2016, Pallidum and lateral ventricle volume enlargement in autism spectrum disorder, Psychiatry Res., 252, 40, 10.1016/j.pscychresns.2016.04.003

Leary, 1996, Moving on: Autism and movement disturbance, Ment. Retard., 34, 39

Noor, 2010, Disruption at the PTCHD1 Locus on Xp22.11 in Autism spectrum disorder and intellectual disability, Sci. Transl. Med., 2, 49, 10.1126/scitranslmed.3001267

Purpura, G., Fulceri, F., Puglisi, V., Masoni, P., and Contaldo, A. (2016). Motor coordination impairment in children with autism spectrum disorder: A pilot study using Movement Assessment Battery for Children-2 Checklist. Minerva. Pediatr., Available online: https://www.minervamedica.it/en/journals/minerva-pediatrica/article.php?cod=R15Y9999N00A16101202.

Christensen, 2016, Prevalence and Characteristics of Autism Spectrum Disorder Among Children Aged 8 Years—Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2012, MMWR Surveill. Summ., 65, 1, 10.15585/mmwr.ss6503a1

Holmboe, 2014, Strong genetic influences on the stability of autistic traits in childhood, J. Am. Acad. Child. Adolesc. Psychiatry, 53, 221, 10.1016/j.jaac.2013.11.001

Taylor, 2017, Etiological influences on the stability of autistic traits from childhood to early adulthood: Evidence from a twin study, Mol. Autism, 8, 5, 10.1186/s13229-017-0120-5

Nakatani, 2009, Abnormal behavior in a chromosome-engineered mouse model for human 15q11-13 duplication seen in Autism, Cell, 137, 1235, 10.1016/j.cell.2009.04.024

Jaramillo, 2016, Altered striatal synaptic function and abnormal behaviour in shank3 Exon4-9 deletion mouse model of Autism, Autism Res., 9, 350, 10.1002/aur.1529

Katayama, 2016, CHD8 haploinsufficiency results in autistic-like phenotypes in mice, Nature, 537, 675, 10.1038/nature19357

Durak, 2016, Chd8 mediates cortical neurogenesis via transcriptional regulation of cell cycle and Wnt signaling, Nat. Neurosci., 19, 1477, 10.1038/nn.4400

Gompers, 2017, Germline Chd8 haploinsufficiency alters brain development in mouse, Nat. Neurosci., 20, 1062, 10.1038/nn.4592

Crawley, 2004, Designing mouse behavioral tasks relevant to autistic-like behaviors, Ment. Retard. Dev. Disabil. Res. Rev., 10, 248, 10.1002/mrdd.20039

He, 2014, Synaptic, transcriptional and chromatin genes disrupted in autism, Nature, 515, 209, 10.1038/nature13772

Vives, 2012, Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations, Nature, 485, 246, 10.1038/nature10989

Neale, 2012, Patterns and rates of exonic de novo mutations in autism spectrum disorders, Nature, 485, 242, 10.1038/nature11011

Talkowski, 2012, Sequencing chromosomal abnormalities reveals neurodevelopmental loci that confer risk across diagnostic boundaries, Cell, 149, 525, 10.1016/j.cell.2012.03.028

Vives, 2012, Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders, Science, 338, 1619, 10.1126/science.1227764

Bernier, 2014, Disruptive CHD8 mutations define a subtype of autism early in development, Cell, 158, 263, 10.1016/j.cell.2014.06.017

Pochareddy, 2015, Targeted DNA sequencing from Autism spectrum disorder brains implicates multiple genetic mechanisms, Neuron, 88, 910, 10.1016/j.neuron.2015.11.009

Nord, 2011, Reduced transcript expression of genes affected by inherited and de novo CNVs in Autism, Eur. J. Hum. Genet., 19, 727, 10.1038/ejhg.2011.24

Halgren, 2012, Corpus callosum abnormalities, intellectual disability, speech impairment, and autism in patients with haploinsufficiency of ARID1B, Clin. Genet., 82, 248, 10.1111/j.1399-0004.2011.01755.x

Santen, 2012, Mutations in SWI/SNF chromatin remodeling complex gene ARID1B cause Coffin-Siris syndrome, Nat. Genet., 44, 379, 10.1038/ng.2217

Kanner, 1943, Autistic disturbances of affective contact, Nerv. Child., 2, 217

Gandal, M.J., Nesbitt, A.M., McCurdy, R.M., and Alter, M.D. (2012). Measuring the maturity of the fast-spiking interneuron transcriptional program in Autism, Schizophrenia, and bipolar disorder. PLoS ONE, 7.

Asada, K., Tojo, Y., Osanai, H., Saito, A., Hasegawa, T., and Kumagaya, S. (2016). Reduced personal space in individuals with Autism spectrum disorder. PLoS ONE, 11.

Matson, 2008, The effects of intellectual functioning on the range of core symptoms of autism spectrum disorders, Res. Dev. Disabil., 29, 341, 10.1016/j.ridd.2007.06.006

McCarthy, 2014, De novo mutations in schizophrenia implicate chromatin remodeling and support a genetic overlap with autism and intellectual disability, Mol. Psychiatry, 19, 652, 10.1038/mp.2014.29

Srivastava, 2014, Intellectual disability and Autism spectrum disorders: Causal genes and molecular mechanisms, Neurosci. Biobehav. Rev., 46, 161, 10.1016/j.neubiorev.2014.02.015

Celen, 2017, Arid1b haploinsufficient mice reveal neuropsychiatric phenotypes and reversible causes of growth impairment, Elife, 6, e25730, 10.7554/eLife.25730

Markram, 2008, Abnormal fear conditioning and amygdala processing in an animal model of Autism, Neuropsychopharmacology, 33, 901, 10.1038/sj.npp.1301453

Horii, 2014, Validation of microinjection methods for generating knockout mice by CRISPR/Cas-mediated genome engineering, Sci. Rep., 4, 4513, 10.1038/srep04513

Ran, 2013, Double nicking by RNA-guided CRISPR Cas9 for enhanced genome editing specificity, Cell, 154, 1380, 10.1016/j.cell.2013.08.021

Shoji, 2014, Contextual and cued fear conditioning test using a video analyzing system in mice, J. Vis. Exp., 1, 85

Bolger, 2014, Trimmomatic: A flexible trimmer for Illumina sequence data, Bioinformatics, 30, 2114, 10.1093/bioinformatics/btu170

Langmead, 2012, Fast gapped-read alignment with Bowtie 2, Nat. Methods, 9, 357, 10.1038/nmeth.1923

Robinson, 2010, A scaling normalization method for differential expression analysis of RNA-seq data, Genome. Biol., 11, R25, 10.1186/gb-2010-11-3-r25

Hagihara, 2014, Transcriptomic evidence for immaturity of the prefrontal cortex in patients with schizophrenia, Mol. Brain, 7, 41, 10.1186/1756-6606-7-41

Murano, 2017, Transcriptomic immaturity of the hippocampus and prefrontal cortex in patients with alcoholism, Sci. Rep., 15, 44531, 10.1038/srep44531

Ginsberg, M.R., Rubin, R.A., Falcone, T., Ting, A.H., and Natowicz, M.R. (2012). Brain transcriptional and epigenetic associations with Autism. PLoS ONE, 7.

Okaty, 2009, Transcriptional and electrophysiological maturation of neocortical fast-spiking GABAergic interneurons, J. Neurosci., 29, 7040, 10.1523/JNEUROSCI.0105-09.2009

Kupershmidt, I., Su, Q.J., Grewal, A., Sundaresh, S., Halperin, I., Flynn, J., Shekar, M., Wang, H., Park, J., and Cui, W. (2010). Ontology-based meta-analysis of global collections of high-throughput public data. PLoS ONE, 5.