論文 - 詳細
| RRC ID | 62857 |
|---|---|
| 著者 | Ueda M, Matsuki T, Fukada M, Eda S, Toya A, Iio A, Tabata H, Nakayama A. |
| タイトル | Knockdown of Son, a mouse homologue of the ZTTK syndrome gene, causes neuronal migration defects and dendritic spine abnormalities. |
| ジャーナル | Mol Brain |
| Abstract |
Zhu-Tokita-Takenouchi-Kim (ZTTK) syndrome, a rare congenital anomaly syndrome characterized by intellectual disability, brain malformation, facial dysmorphism, musculoskeletal abnormalities, and some visceral malformations is caused by de novo heterozygous mutations of the SON gene. The nuclear protein SON is involved in gene transcription and RNA splicing; however, the roles of SON in neural development remain undetermined. We investigated the effects of Son knockdown on neural development in mice and found that Son knockdown in neural progenitors resulted in defective migration during corticogenesis and reduced spine density on mature cortical neurons. The induction of human wild-type SON expression rescued these neural abnormalities, confirming that the abnormalities were caused by SON insufficiency. We also applied truncated SON proteins encoded by disease-associated mutant SON genes for rescue experiments and found that a truncated SON protein encoded by the most prevalent SON mutant found in ZTTK syndrome rescued the neural abnormalities while another much shorter mutant SON protein did not. These data indicate that SON insufficiency causes neuronal migration defects and dendritic spine abnormalities, which seem neuropathological bases of the neural symptoms of ZTTK syndrome. In addition, the results support that the neural abnormalities in ZTTK syndrome are caused by SON haploinsufficiency independent of the types of mutation that results in functional or dysfunctional proteins. |
| 巻・号 | 13(1) |
| ページ | 80 |
| 公開日 | 2020-5-24 |
| DOI | 10.1186/s13041-020-00622-4 |
| PII | 10.1186/s13041-020-00622-4 |
| PMID | 32448361 |
| PMC | PMC7245844 |
| MeSH | Abnormalities, Multiple / genetics* Animals Brain / metabolism Cell Movement* DNA-Binding Proteins / genetics* DNA-Binding Proteins / metabolism Dendritic Spines / pathology* Gene Knockdown Techniques* HEK293 Cells Humans Mice Mutation / genetics Nuclear Proteins / genetics* Nuclear Proteins / metabolism Pyramidal Cells / metabolism Syndrome |
| IF | 4.686 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | 293(RCB1637) |