2007 Fiscal Year Final Research Report Summary
Analysis of Mutation Affecting Liver Function and Regeneration in Model Organisms
| Project/Area Number |
18390021
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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 |
Biological pharmacy
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
NISHINA Hiroshi Tokyo Medical and Dental University, Medical Research Institute, Professor (60212122)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAMURA Takashi Tokyo Medical and Dental University, Medical Research Institute, Assistant Professor (80431948)
ASAOKA Yoichi Tokyo Medical and Dental University, Medical Research Institute, Assistant Professor (10436644)
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| Project Period (FY) |
2006 – 2007
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| Keywords | liver / development / regeneration / model organism / medaka / knockout mice / MAP kinase / SAPK / JNK |
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| Research Abstract |
The liver is an organ with vital functions, including processing and storage of nutrients, maintenance of serum composition, detoxification and bile production. Recently, several genes that are crucial for liver formation and function have been isolated in mice and confirmed by reverse genetics. Although a reverse genetic approach is powerful in characterizing function of known genes, knowledge of genes in liver formation and disease is still limited. Therefore, identifying mutations affecting these aspects will uncover genes required for these processes. Systematic forward genetic screens for mutations affecting liver formation and function such as hepatic bud formation, liver morphogenesis, bile color in the gall bladder, lipid metabolism, and liver laterality have been carried out in Medaka, Oryzias latipes. To isolate mutants that model human liver diseases, we are analyzing these mutations. Among them, kendama (ken) mutation was isolated as a gene that affects the laterality of the liver. ken mutant was viable and fertile with inverted positions of liver and heart, and with inverted spiral of gut. Interestingly, the spleen was almost lost in ken mutant. This phenotype is very similar to human genetic disease 'asplenia' whose gene mutation is still unknown. Furthermore, white livers consisting of bloated and Oil red O-positive hepatocytes were observed in ken mutants. Thus, ken mutation models human disease asplenia and Non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH). Especially, NAFLD and NASH are serious human diseases in the modern world, so ken mutation may shed a new light on the molecular mechanisms of these diseases and the preventive medicine.
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[Journal Article] Osteoclastic estrogen receptor alpha mediates the osteoprotective estrogen action through Fas ligand signaling2007
Author(s)
Nakamura, T., Imai, Y., Matsumoto, T., Sato, S., Takeuchi, K., Igarashi, K., Harada, Y., Azuma, Y., Krust. A., Yamamoto, Y., Nishina, H., Takeda, S., Takayanagi, H., Metzger, D., Kanno. J., Takaoka, K., Martin, TJ., Chambon, P., Kato, S.
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Journal Title
Description
「研究成果報告書概要(欧文)」より
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