| RRC ID |
87182
|
| 著者 |
Fujita Y, Masuda K, Bando M, Nakato R, Katou Y, Tanaka T, Nakayama M, Takao K, Miyakawa T, Tanaka T, Ago Y, Hashimoto H, Shirahige K, Yamashita T.
|
| タイトル |
Decreased cohesin in the brain leads to defective synapse development and anxiety-related behavior.
|
| ジャーナル |
J Exp Med
|
| Abstract |
Abnormal epigenetic regulation can cause the nervous system to develop abnormally. Here, we sought to understand the mechanism by which this occurs by investigating the protein complex cohesin, which is considered to regulate gene expression and, when defective, is associated with higher-level brain dysfunction and the developmental disorder Cornelia de Lange syndrome (CdLS). We generated conditional Smc3-knockout mice and observed greater dendritic complexity and larger numbers of immature synapses in the cerebral cortex of Smc3+/- mice. Smc3+/- mice also exhibited more anxiety-related behavior, which is a symptom of CdLS. Further, a gene ontology analysis after RNA-sequencing suggested the enrichment of immune processes, particularly the response to interferons, in the Smc3+/- mice. Indeed, fewer synapses formed in their cortical neurons, and this phenotype was rescued by STAT1 knockdown. Thus, low levels of cohesin expression in the developing brain lead to changes in gene expression that in turn lead to a specific and abnormal neuronal and behavioral phenotype.
|
| 巻・号 |
214(5)
|
| ページ |
1431-1452
|
| 公開日 |
2017-5-1
|
| DOI |
10.1084/jem.20161517
|
| PII |
jem.20161517
|
| PMID |
28408410
|
| PMC |
PMC5413336
|
| MeSH |
Animals
Anxiety / etiology*
Anxiety / physiopathology
Brain / metabolism
Brain / physiopathology*
Brain Chemistry / physiology
Cell Cycle Proteins / deficiency*
Cell Cycle Proteins / physiology
Chondroitin Sulfate Proteoglycans / physiology
Chromosomal Proteins, Non-Histone / deficiency*
Chromosomal Proteins, Non-Histone / physiology
Cohesins
Female
Gene Expression Regulation / physiology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Synapses / physiology*
|
| リソース情報 |
| 実験動物マウス |
RBRC01828 |
