Reference - Detail
| RRC ID | 58490 |
|---|---|
| Author | Matsumura K, Seiriki K, Okada S, Nagase M, Ayabe S, Yamada I, Furuse T, Shibuya H, Yasuda Y, Yamamori H, Fujimoto M, Nagayasu K, Yamamoto K, Kitagawa K, Miura H, Gotoda-Nishimura N, Igarashi H, Hayashida M, Baba M, Kondo M, Hasebe S, Ueshima K, Kasai A, Ago Y, Hayata-Takano A, Shintani N, Iguchi T, Sato M, Yamaguchi S, Tamura M, Wakana S, Yoshiki A, Watabe AM, Okano H, Takuma K, Hashimoto R, Hashimoto H, Nakazawa T. |
| Title | Pathogenic POGZ mutation causes impaired cortical development and reversible autism-like phenotypes. |
| Journal | Nat Commun |
| Abstract |
Pogo transposable element derived with ZNF domain (POGZ) has been identified as one of the most recurrently de novo mutated genes in patients with neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD), intellectual disability and White-Sutton syndrome; however, the neurobiological basis behind these disorders remains unknown. Here, we show that POGZ regulates neuronal development and that ASD-related de novo mutations impair neuronal development in the developing mouse brain and induced pluripotent cell lines from an ASD patient. We also develop the first mouse model heterozygous for a de novo POGZ mutation identified in a patient with ASD, and we identify ASD-like abnormalities in the mice. Importantly, social deficits can be treated by compensatory inhibition of elevated cell excitability in the mice. Our results provide insight into how de novo mutations on high-confidence ASD genes lead to impaired mature cortical network function, which underlies the cellular pathogenesis of NDDs, including ASD. |
| Volume | 11(1) |
| Pages | 859 |
| Published | 2020-2-26 |
| DOI | 10.1038/s41467-020-14697-z |
| PII | 10.1038/s41467-020-14697-z |
| PMID | 32103003 |
| PMC | PMC7044294 |
| MeSH | Adolescent Animals Autistic Disorder / genetics* Behavior, Animal Brain / pathology Cell Differentiation Cell Line Cell Proliferation Female Gene Editing Gene Knockdown Techniques Genetic Predisposition to Disease / genetics* Heterozygote Humans Intellectual Disability Male Malformations of Cortical Development / genetics* Mice Mice, Inbred C57BL Middle Aged Mutation* Neurodevelopmental Disorders / genetics Neurogenesis Neurons / metabolism Phenotype* Transposases / genetics* |
| IF | 12.121 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 33 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| DNA material | T7-NLS hCas9-pA (RDB13130) |