2006 Fiscal Year Final Research Report Summary
Abnormal development of the central nervous system of the knockout mouse that becomes obese
| Project/Area Number |
17590168
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General anatomy (including Histology/Embryology)
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| Research Institution | Yokohama City University |
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Principal Investigator |
IKEDA Yayoi Yokohama City University, School of Medicine, Associate Professor, 医学部, 準教授 (00202903)
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| Co-Investigator(Kenkyū-buntansha) |
IKEDA Masaaki Tokyo Medical and Dntal University Graduate School, Associate Professor, 大学院医歯学総合研究科, 助教授 (20193211)
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| Project Period (FY) |
2005 – 2006
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| Keywords | nuclear receptor / ventromedial hypothalamus / Steroidogenic factor 1 (SF-1) / obesity / central nervous system / conditional knockout |
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| Research Abstract |
Steroidogenic factor 1 (SF-1) is an orphan nuclear receptor that plays key roles in adrenal and gonadal development, expression of pituitary gonadotropins, and development of the ventromedial hypothalamic nucleus (VMH). If kept alive by adrenal transplantation, SF-1 knockout (KO) mice develop a metabolic syndrome characterized by delayed-onset obesity and decreased locomotor activity, with no change in food consumption. To define specific roles of SF-1 in the VMH, we used the Cre-loxP system to inactivate SF-1 in a CNS-specific manner. Using the nestin-Cre transgene, which inactivates SF-1 during embryogenesis, we largely recapitulated the VMH structural defect seen in the global SF-1 KO mice. These CNS-specific SF-1 KO mice had decreased locomotor activity and became obese on a high-fat diet. In behavioral tests felt to measure anxiety, they were significantly more "anxious" than wild-type littermates. In addition, CNS-specific SF-1 KO mice had considerably decreased expression in the region of the VMH of several genes, including brain-derived neurotrophic factor (BDNF), the type 2 receptor for corticotropin-releasing hormone (CRF-R_2), and the leptin receptor. These findings reveal important roles of SF-1 in the hypothalamic expression of key regulators of body weight and anxiety, providing a plausible molecular explanation for the phenotype caused by CNS-specific KO of SF-1.
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[Journal Article] Ubc9 and protein inhibitor of activated STAT 1 activate Chicken Ovalbumin Upstream Promoter-Transcription Factor I-mediated human CYP11B2 gene transcription2005
Author(s)
Kurihara, I., Shibata, H., Kobayashi, S., Suda, N., Ikeda, Y., Yokota, K., Murai, A., Saito, I., Rainey, W.E., Saruta, T.
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Journal Title
J.Biol.Chem. 280
Pages: 6721-6730
Description
「研究成果報告書概要(欧文)」より
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