Association analysis of the molecular basis of brain development and mouse behavior using CAMDI knockout mice
| Project/Area Number |
26460495
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Experimental pathology
|
|---|
| Research Institution | Tokyo University of Pharmacy and Life Science |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2014-04-01 – 2017-03-31
|
| Project Status |
Completed (Fiscal Year 2016)
|
| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
|---|
| Keywords | CAMDI / HDAC6 / 自閉症 / 中心体 / 治療 / 細胞移動 / アセチル化 / 行動 / 回復 / DISC1 / 統合失調症 / モノアミン |
|---|
| Outline of Final Research Achievements |
CAMDI has been suggested to promote radial migration through centrosome regulation. However, its physiological relevance is unclear. We report the generation and characterization of CAMDI-deficient mice. CAMDI-deficient mice exhibit delayed radial migration with aberrant neural circuit formation and psychiatric behaviors including hyperactivity, repetitive behavior, and social abnormality typically observed in autism spectrum disorder patients. Analyses of direct targets of CAMDI identify HDAC6 whose a-tubulin deacetylase activity is inhibited by CAMDI at the centrosome. CAMDI deficiency increases HDAC6 activity, leading to unstable centrosomes with reduced c-tubulin and acetylated α-tubulin levels. Most importantly, psychiatric behaviors as well as delayed migration are significantly rescued by treatment with Tubastatin A, a specific inhibitor of HDAC6.
|
Report
(4 results)
Research Products
(8 results)
-
[Journal Article] Rescue of CAMDI deletion-induced delayed radial migration and psychiatric behaviors by HDAC6 inhibitor.2016
Author(s)
Fukuda, T., Nagashima, S., Abe, T., Kiyonari, H., Inatome, R. and Yanagi, S.
-
Journal Title
EMBO. Rep.
Volume: 17
Issue: 12
Pages: 1785-1798
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
-
[Journal Article] Downregulation of Centaurin gamma1A increases synaptic transmission at Drosophila larval neuromuscular junctions2014
Author(s)
Homma, M.、 Nagashima, S., Fukuda, T., Yanagi, S., Miyakawa, H., Suzuki, E., Morimoto, T.
-
Journal Title
Europian Journal of Neuroscience
Volume: VOL40
Issue: 8
Pages: 3158-3170
DOI
Related Report
Peer Reviewed
-
-
-
-
-
-
