Team for Advanced Development and Evaluation of Human Disease Models

To augment the value of human disease model mutant mouse as resource used for developing diagnosis, treatment, and the drug development, the identification and the analyses of the responsible gene mutations should be indispensable. In addition, detailed information on the phenotype based on the molecular mechanism that may correspond to the conditions of the human disease brings further both basic and practical values. Our team develops advanced mouse phenotype analysis technologies to reveal and augment those values of various mutant mice by addition of novel phenotype information. Moreover, for human cancer model mice, advanced pathological technologies including in-situ histology analysis, genome and epigenome analysis, transcriptome analysis will be applied to enhance the values as cancer models.

Research Subjects

• Development of advanced technologies for phenotypic analysis of human disease model mouse.---NMR Metabolome analysis
• Establishment of mouse models utilized for innovative cancer drug discovery
• Establishment and analysis of novel mouse model of deafness

Publications

1. Yao R., Natsume Y., Saiki Y., Shioya H., Takeuchi K., Yamori T., Toki H., Aoki I., Saga T., Noda T.:
   "Disruption of Tacc3 function leads to in vivo tumor regression"
   Oncogene advance online publication, June 20, 2011; doi:10.1038/onc.2011.235, 1-14 (2011)
2. Tokuzawa Y, Yagi K, Yamashita Y, Nakachi Y, Nikaido I, Bono H, Ninomiya Y, Kanesaki-Yatsuka Y, Akita M, Motegi H, Wakana S, Noda T, Sablitzky F, Arai S, Kurokawa R, Fukuda T, Katagiri T, Schönbach C, Suda T, Mizuno Y, Okazaki Y.:
   "Id4, a new candidate gene for senile osteoporosis, acts as a molecular switch promoting osteoblast differentiation."
   PLoS Genet. 6(7):e1001019. (2010)
3. Tanaka N., Waki K., Kaneda H., Suzuki T., Yamada I., Furuse T., Kobayashi K., Motegi H., Toki H., Inoue M., Minowa O., Noda T., Takao K., Miyakawa T., Takahashi A., Koide T., Wakana S., Masuya H.:
   "SDOP-DB: A comparative standardized-protocol database for mouse phenotypic analyses"
   Bioinformatics, 26(8):1133-1134 (2010)
4. Furuse T., Wada Y., Hattori K., Yamada I., Kushida T., Shibukawa Y., Masuya H., Kaneda H., Miura I., Seno N., Kanda T., Hirose R., Toki S., Nakanishi K., Kobayashi K., Sezutsu H., Gondo Y., Noda T., Yuasa S., Wakana S.:
   "Phenotypic characterization of a new Grin1 mutant mouse generated by ENU mutagenesis"
   European Journal of Neuroscience, 31:1281-1291 (2010)
5. Sato H., Suzuki T., Ikeda K., Masuya H., Sezutsu H., Kaneda H., Kobayashi K., Miura I., Kurihara Y., Yokokura S., Nishida K., Tamai M., Gondo Y., Noda T., Wakana S.:
   "A monogenic dominant mutation in Rom1 generated by N-ethyl-N-nitrosourea mutagenesis causes retinal degeneration in mice"
   Molecular Vision, 16:378-391 (2010)
6. Watanabe T, Kubota N, Ohsugi M, Kubota T, Takamoto I, Iwabu M, Awazawa M, Katsuyama H, Hasegawa C, Tokuyama K, Moroi M, Sugi K, Yamauchi T, Noda T, Nagai R, Terauchi Y, Tobe K, Ueki K, Kadowaki T.:
   "Rimonabant ameliorates insulin resistance via both adiponectin-dependent and adiponectin-independent pathways."
   J Biol Chem. 2009 Jan 16;284(3):1803-12. Epub 2008 Nov 13.
7. Ajima R., Akiyama T., Usui M., Yoneda M., Yoshida Y., Nakamura T., Minowa O., Noda M., Tanaka S., Noda T., Yamamoto T.:
   "Osteoporotic bone formation in mice lacking tob2; involvement of Tob2 in RANK ligand expression and osteoclasts differentiation."
   FEBS Letters, 582(9):1313-1318 (2008).
8. Shigeyama Y., Kobayashi T., Kido Y., Hashimoto N., Asahara S., Matsuda T., Takeda A., Inoue T., Shibutani Y., Koyanagi M., Uchida T., Inoue M., Hino O., Kasuga M., Noda T.:
   "Biphasic response of pancreatic beta-cell mass to ablation of tuberous sclerosis complex 2 in mice."
   Mol Cell Biol. 28(9):2971-2979 (2008).
9. Sakuraba Y, Kimura T, Masuya H, Noguchi H, Sezutsu H, Takahasi KR, Toyoda A, Fukumura R, Murata T, Sakaki Y, Yamamura M, Wakana S, Noda T, Shiroishi T, Gondo Y.:
   "Identification and characterization of new long conserved noncoding sequences in vertebrates."
   Mamm Genome. 2008 Oct-Dec;19(10-12):703-12.
10. Dohi Y, Ikura T, Hoshikawa Y, Katoh Y, Ota K, Nakanome A, Muto A, Omura S, Ohta T, Ito A, Yoshida M, Noda T, Igarashi K.:
    "Bach1 inhibits oxidative stress-induced cellular senescence by impeding p53 function on chromatin."
    Nat Struct Mol Biol. 2008 Dec;15(12):1246-54. Epub 2008 Nov 16.