2007 Fiscal Year Final Research Report Summary
Neuronal development and synaptic plasticity in Cdc42 cenditional knockout mice
| 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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| Keywords | Cdc42 / knockout mice / Rho family / cerebral cortex / cerebellum |
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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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Research Products
(16 results)
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[Journal Article] Semaphorin 3F confines ventral tangential migration of lateral olfactory tract neurons onto telencephalon surface2008
Author(s)
Ito, K., Kawasaki, T., Takashima, S., Matsuda, I., Aiba., A., Hirata, T
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Journal Title
J. Neurosci 28-17
Pages: 4414-4422
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] protein-independent neuromodulatory action of adenosine on metabotropic glutamate signaling in mouse cerebellar Purkinje Cells2007
Author(s)
Tabata, T., Kawakami, D., Hashimoto, K., Kassai, H., Yoshida, T., Hashimotodani, Y., Fredholm, B. B., Seikno, Y., Aiba, A., Kano, M. G
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Journal Title
J. Physiol 581-2
Pages: 693-708
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] The M-Ras-RA-GEF-2-Rapl pathway mediates tumor necrosis factor-a-dependent regulation of integrin activation in splenocytes2007
Author(s)
Yoshikawa, Y., Satoh, T., Tamura, T., Wei, P., Bilasy, S. E., Edamatsu, H., Aiba., A., Katagiri, K., Kinashi, T., Nakao, K., Kataoka, T
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Journal Title
Mol. Biol. Cell 18-8
Pages: 2949-2959
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Defective vascular morphogenesis and mid-gestation embryonic death in mice lacking RA-GEF-12007
Author(s)
Wei, P., Satoh, T., Edamatsu, H., Aiba, A., Setsu, T., Terashima, T., Kitazawa, S., Nakao, K., Yoshikawa, Y., Tamada, M., Kataoka, T
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Journal Title
Biochem.Biophys.Res.Commun 363-1
Pages: 106-112
Description
「研究成果報告書概要(欧文)」より
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