| Project/Area Number |
18300106
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neuroscience in general
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| Research Institution | Kobe University |
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Principal Investigator |
AIBA Atsu Kobe University, Graduate School of Medicine, Professor (20271116)
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| Co-Investigator(Kenkyū-buntansha) |
HARADA Takeshi Kobe University, Graduate School of Medicine, Assistant Professor (30362768)
KASSAI Hidetoshi Kobe University, Graduate School of Medicine, Assistant Professor (40403232)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥16,450,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥1,950,000)
Fiscal Year 2007: ¥8,450,000 (Direct Cost: ¥6,500,000、Indirect Cost: ¥1,950,000)
Fiscal Year 2006: ¥8,000,000 (Direct Cost: ¥8,000,000)
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| Keywords | Cdc42 / knockout mice / Rho family / cerebral cortex / cerebellum / cdc42 / Cre / Ella-Cre |
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| Research Abstract |
In order to investigate the role of Rho family GTPase, Cdc42, in synapse formation and maintenance, synaptic plasticity, and leaning, we generated Cdc42 conditional knockout mice. We introduced loxP sequences into cdc42 allele by gene targeting in the embryonic stem cells. Then we generated flox-Cdc42 mice by using the mutant ES cells. By crossing flox-Cdc42 mice with two different neuron-specific Cre lines, we generated two distinct neuron-specific Cdc42 knockout lines.
(1) Forebrain-specific Cdc42 knockout (FB-Cdc42 KO) mice
To avoid embryonic lethality, we have disrupted cdc42 gene via Cre-loxP recombination using Emx1-Cre mice. Emx1 promoter/enhancer induces Cre recombinase expression exclusively in the dorsal telencephalon as early as embryonic day (E) 10.5, tcogehereby eliminating Cdc42 expression in cortical projection neurons from the beginning of cerebral cortinesis. Western blot analysis of the protein prepared from FB-Cdc42 KO cerebral cortex showed that Cdc42 was knocked down in the KO cerebral cortex. We have found expanded cerebral cortex with abnormal layer formation in the FB-Cdc42 KO mice. Furthermore, the morphology of hippocampus was severely distorted in the FB-Cdc42 KO mice. These results suggested that Cdc42 controls the cell proliferation and differentiation of the neuron during cortical development.
(2) Purkinje cell specific Cdc42 knockout (PC-Cdc42 KO) mice
To investigate the role of Cdc42 in cerebellar Purkinje cells, we have disrupted cdc42 gene using L7-Cre mice. PC-Cdc42 KO mice did not show ataxic gait. The histological analysis of the PC-Cdc42 KO cerebellum showed no apparent abnormality in morphology of the Purkinje cell dendrites.
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