| RRC ID |
49499
|
| 著者 |
Hamada N, Negishi Y, Mizuno M, Miya F, Hattori A, Okamoto N, Kato M, Tsunoda T, Yamasaki M, Kanemura Y, Kosaki K, Tabata H, Saitoh S, Nagata KI.
|
| タイトル |
Role of a heterotrimeric G-protein, Gi2, in the corticogenesis: possible involvement in periventricular nodular heterotopia and intellectual disability.
|
| ジャーナル |
J Neurochem
|
| Abstract |
We analyzed the role of a heterotrimeric G-protein, Gi2, in the development of the cerebral cortex. Acute knockdown of the α-subunit (Gαi2) with in utero electroporation caused delayed radial migration of excitatory neurons during corticogenesis, perhaps because of impaired morphology. The migration phenotype was rescued by an RNAi-resistant version of Gαi2. On the other hand, silencing of Gαi2 did not affect axon elongation, dendritic arbor formation or neurogenesis at ventricular zone in vivo. When behavior analyses were conducted with acute Gαi2-knockdown mice, they showed defects in social interaction, novelty recognition and active avoidance learning as well as increased anxiety. Subsequently, using whole-exome sequencing analysis, we identified a de novo heterozygous missense mutation (c.680C>T; p.Ala227Val) in the GNAI2 gene encoding Gαi2 in an individual with periventricular nodular heterotopia and intellectual disability. Collectively, the phenotypes in the knockdown experiments suggest a role of Gαi2 in the brain development, and impairment of its function might cause defects in neuronal functions which lead to neurodevelopmental disorders.
|
| 巻・号 |
140(1)
|
| ページ |
82-95
|
| 公開日 |
2017-1-1
|
| DOI |
10.1111/jnc.13878
|
| PMID |
27787898
|
| MeSH |
Animals
Avoidance Learning / physiology
COS Cells
Cerebral Cortex / diagnostic imaging
Cerebral Cortex / growth & development*
Cerebral Cortex / metabolism*
Chlorocebus aethiops
Female
GTP-Binding Protein alpha Subunit, Gi2 / deficiency
GTP-Binding Protein alpha Subunit, Gi2 / physiology*
Humans
Intellectual Disability / diagnostic imaging
Intellectual Disability / genetics
Intellectual Disability / metabolism*
Mice
Mice, Inbred ICR
Mice, Knockout
Periventricular Nodular Heterotopia / diagnostic imaging
Periventricular Nodular Heterotopia / genetics
Periventricular Nodular Heterotopia / metabolism*
Pregnancy
|
| IF |
4.066
|
| 引用数 |
5
|
| リソース情報 |
| 遺伝子材料 |
pCAG-Myc-mG alpha i2 (RDB15368)
pCAG-Myc-mG alpha i1 (RDB15369)
pCAG-Myc-mG alpha i3 (RDB15370)
pCAG-Myc-mG alpha o1 (RDB15371). |
