Hiroshi Mitani / Professor / Division of Biosciences
Department of Integrated Biosciences / / Mechanisms of vertebrate genome stability using Medaka as a model system

Career Summary
1979: Graduated, Zoological Institute Faculty of Science, University of Tokyo
1985: Doctor of Science from The University of Tokyo
1985: Research Associate, the Department of Experimental Radiology Faculty of Medicine, Kyoto University
1986: Instructor, Zoological Institute Faculty of Science, University of Tokyo
1990: Lecturer, Zoological Institute School of Science, University of Tokyo
1994: Associate Professor, Department of Biosciences School of Science, University of Tokyo
1998: Visiting Associate Professor, Radiation Biology Center Kyoto University (to 2001)
1999: Associate Professor, Department of Integrated Biosciences Graduate School of Frontier Sciences, University of Tokyo
2003: Professor, Department of Integrated Biosciences Graduate School of Frontier Sciences, University of Tokyo
Educational Activities
Graduate School: Genomic Instability, Breakthrough Now and Then, Basic Biochemistry and Molecular Biology, Statistical Analysis for Biosciences
Research Activities
The genome encodes whole hereditary information in the DNA. Genome instability is caused by a great variety of DNA-damaging agents, such as radiation ultraviolet (UV) light, reactive oxygen species, and metabolites that can act as alkylating agents. Mutations with subtle effects on cell physiology may play a major role in biological adaptation and genome evolution. Genome maintenance mechanisms, including DNA repair checkpoint regulation and apoptosis, are preventing cancer, premature ageing and other diseases. The study of genome stability is fundamental to understanding the function of the cell in vivo.
Medaka (Oryzias latipes) has been widely used as an experimental animal because of its relatively short life cycle, high fecundity, transparent egg chorion, and small size. It is an important test system for environmental research, cancer research, and developmental biology. I use medaka as a model system to elucidate the molecular mechanisms of genome stability. We identified radiation-sensitive mutants from populations of ENU-mutagenized medaka that show high incidence of radiation-induced curly tailed (ric) malformations after low doses of irradiation. One mutant strain has a defect in the rapid repair of DNA double-strand breaks. These results support the usefulness of medaka mutants for investigating various biological consequences of DNA double-strand breaks in vivo and for sensitive monitoring of genotoxicity related to low-dose radiation. Currently, our main research focus is using GFP-transgenic fish to analyze cellular responses and mutagenesis in vivo after exposure of DNA damaging stress.
More than 100 wild populations (northern and southern Japanese populations, China/West Korea and East Korea populations), and other strains have been maintained as closed colonies since 1985. Preliminary geographic surveys on these wild population colonies are revealing the wide variation in their quantitative traits and DNA polymorphisms, including many substitutions of amino acids in coding regions. These medaka stocks with genomic diversity would prove to be a cornucopia in the `post-genome sequencing' era.
Mitani, H., Kamei, Y., Fukamachi, S., Oda, S., Sasaki, T., Asakawa, S., Todo, T., Shimizu ,N. (2006) The Medaka Genome: Why we need the multiple fish models in vertebrate functional genomics. Genome Dynamics vol. 2."Structure and Evolution of Vertebrate Genomes" Edited by Volff JN. Karger Publishers, Basel p.165-182.

Fukamachi, S., Wakamatsu, Y., and Mitani, H. (2006) Medaka double mutants for color interfere and leucophore free: characterization of the xanthophore-somatolactin relationship using the leucophore free gene. Dev. Genes Evol. 216, 152-157.

Sasaki, T., Shimizu, A., Ishikawa, S. K., Imai, S., Asakawa, S. ,Murayama, Y., Khorasani, M. Z., Mitani,H., Furutani-Seiki, M., Kondoh, H., Nanda, I., Schmid, M., Schartl, M., Nonaka, M., Takeda, H., Hori, H., Himmelbauer, H., Shima, A. and Shimizu, N. (2006) The DNA sequence of medaka chromosome LG22. Genomics, 89, 124-133.

Fukamachi, S., Yada, T., and Mitani, H., (2005) Medaka receptors for somatolactin and growth hormone: phylogenetic paradox among fish growth hormone receptors. Genetics, 171, 1875-1883.

Aizawa, K., Mitani, H., Kogure, N., Shimada, A., Hirose, Y., Sasado, T., Morinaga, C., Yasuoka, A., Yoda, H., Watanabe, T., Iwanami, N., Kunimatsu, S., Osakada, M., Suwa, H., Niwa, K., Deguchi, T., Hennrich, T., Todo, T., Shima, A., Kondo, H., Furutani-Seiki, M. (2004) Identification of radiation-sensitive mutants in the Medaka, Oryzias latipes Mechanisms of Development 21, 895-902.

Naruse, K., Tanaka, K., Mita, K., Shima, A., Postlethwait, J., Mitani, H., (2004) A Medaka Gene Map: The trace of ancestral vertebrate proto-chromosomes revealed by comparative gene mapping. Genome Res 14, 820-826.
Other Activities
The Japan Radiation Research Society (Committee·Exucectives 2003-2007)The Zoological Society of JapanThe Molecular Biology Society of Japan The Society of Evolutionary Studies, Japan
Future Plan
Messages to Students