1. マウスES細胞で遺伝子の両アレルを迅速に破壊する方法の開発
2. ES細胞の多能性の制御機構
3. 体細胞からiPS細胞へのreprogrammingの機構
4. トランスポゾンを用いた変異マウス作製法の開発
5. ヒト疾患モデルマウスの作製と解析

最近の論文:

Horie K., C. Kokubu, J. Yoshida, K. Akagi, A. Isotani, A. Oshitani, K. Yusa, R. Ikeda, Y. Huang, A. Bradley, J. Takeda. A homozygous mutant embryonic stem cell bank applicable for phenotype-driven genetic screening. Nat. Methods, in press.

LaRocque J.R., J.M. Stark, J. Oh, E. Bojilova, K. Yusa, K. Horie, J. Takeda, M. Jasin. Interhomolog recombination and loss of heterozygosity in wild-type and Bloom syndrome helicase (BLM)-deficient mammalian cells. Proc. Natl. Acad. Sci. USA 108: 11971-11976, 2011.

Okada I., H. Hamanoue, K. Terada, T. Tohma, A. Megarbane, E. Chouery, J. Abou-Ghoch, N. Jalkh, O. Cogulu, F. Ozkinay, K. Horie, J. Takeda, T. Furuichi, S. Ikegawa, K. Nishiyama, S. Miyatake, A. Nishimura, T. Mizuguchi, N. Niikawa, F. Hirahara, T. Kaname, K. Yoshiura, Y. Tsurusaki, H. Doi, N. Miyake, T. Furukawa, N. Matsumoto, H. Saitsu. SMOC1 is essential for ocular and limb development in humans and mice. Am. J. Hum. Genet. 88: 30-41, 2011.

Horie K., G. Gaitanaris, A. Gragerov. Selection of targeted mutants from a library of randomly mutagenized ES cells. Methods Mol. Biol. 693: 283-294, 2011.

Kakefuda K., A. Oyagi, M. Ishisaka, K. Tsuruma, M. Shimazawa, K. Yokota, Y. Shirai, K. Horie, N. Saito, J. Takeda, H. Hara. Diacylglycerol kinase β knockout mice exhibit lithium-sensitive behavioral abnormalities. PLoS One 5: e13447, 2010.

Horie K., C. Kokubu, J. Takeda. Functional genomics in the mouse using the sleeping beauty transposon system. Methods Enzymol. 477: 71-89. 2010.

Shirai Y., T Kouzuki, K. Kakefuda, S. Moriguchi, A. Oyagi, K. Horie, S.Y. Morita, M. Shimazawa, K. Fukunaga, J. Takeda, N. Saito, H. Hara. Essential role of neuron-enriched diacylglycerol kinase (DGK), DGKbeta in neurite spine formation, contributing to cognitive function. PLoS One . 5: e11602, 2010.

Yagita K., K. Horie, S. Koinuma, W. Nakamura, I. Yamanaka, A. Urasaki, Y. Shigeyoshi, K. Kawakami, S. Shimada, J. Takeda, Y. Uchiyama. Development of the circadian oscillator during differentiation of mouse embryonic stem cells in vitro. Proc. Natl. Acad. Sci. USA 107: 3846-3851, 2010.

Kokubu C., K. Horie, K. Abe, R. Ikeda, S. Mizuno, Y. Uno, S. Ogiwara, M. Ohtsuka, A. Isotani, M. Okabe, K. Imai, J. Takeda. A transposon-based chromosomal engineering method to survey a large cis-regulatory landscape in mice. Nat. Genet. 41: 946-952, 2009.

Kitada, K., V.W. Keng, J. Takeda, K. Horie. Generating mutant rats using the Sleeping Beauty transposon system. Methods 49: 236-242, 2009.

Saito, E.S., V.W. Keng, J. Takeda, K. Horie. Translation from nonautonomous type IAP retrotransposon is a critical determinant of transposition activity: implication for retrotransposon-mediated genome evolution. Genome Res. 18: 859-868, 2008.

Zeng H. *, K. Horie* (*equal contribution), L. Madisen, M.N. Pavlova, G. Gragerova, A.D. Rohde, B.A. Schimpf, Y. Liang, E. Ojala, F. Kramer, P. Roth, O. Slobodskaya, I. Dolka, E.A. Southon, L. Tessarollo, K.E. Bornfeldt, A. Gragerov, G.N. Pavlakis, G.A. Gaitanaris. An inducible and reversible mouse genetic rescue system. PLoS Genet. 4: e1000069, 2008.

Takeda J., V.W. Keng, K. Horie ; Germline mutagenesis mediated by Sleeping Beauty transposon system in mice. Genome Biol. 18: 859-868, 2008 (Review).

Gragerov A.*, K. Horie* (*equal contribution), M. Pavlova, L. Madisen, H. Zeng, G. Gragerova, A. Rhode, I. Dolka, P. Roth, A. Ebbert, S. Moe, C. Navas, E. Finn, J. Bergmann, D.K. Vassilatis, G.N. Pavlakis, G.A. Gaitanaris. A large scale, saturating insertional mutagenesis of the mouse genome. Proc. Natl. Acad. Sci. USA 104: 14406-14411, 2007.

Horie K., E.S. Saito, V.W. Keng, R. Ikeda, H. Ishihara, Takeda J. Retrotransposons influence the mouse transcriptome: implication for the divergence of genetic traits. Genetics. 176: 815-827, 2007.

Kitada K, S. Ishishita, K. Tosaka, R. Takahashi, M. Ueda, V.W. Keng, K. Horie, J. Takeda. Transposon-tagged mutagenesis in the rat. Nat. Methods. 4: 131-133, 2007.

Ikeda R., C. Kokubu, K. Yusa, V.W. Keng, K. Horie, J. Takeda. Sleeping Beauty transposase has an affinity for heterochromatin conformation. Mol. Cell. Biol. 27: 1665-1676, 2007.

Yae K., V.W. Keng, M. Koike, K. Yusa, M. Kouno, Y. Uno, G. Kondoh, T. Gotow, Y. Uchiyama, K. Horie, J. Takeda. Sleeping Beauty transposon-based phenotypic analysis of mice: lack of Arpc3 results in defective trophoblast outgrowth. Mol. Cell. Biol. 26: 6185-6196, 2006.

Hayakawa T., K. Yusa, M. Kouno, J. Takeda, K. Horie. Bloom's syndrome gene-deficient phenotype in mouse primary cells induced by a modified tetracycline-controlled trans-silencer. Gene. 369: 80-89, 2006.

Keng V.W., K. Yae, T. Hayakawa, S. Mizuno, Y. Uno, K. Yusa, C. Kokubu, T. Kinoshita, K. Akagi, N.A. Jenkins, N.G. Copeland, K. Horie, J. Takeda. Region-specific saturation germline mutagenesis in mice using the Sleeping Beauty transposon system. Nat. Methods. 2: 763-769, 2005.

Liu G., A.M. Geurts, K. Yae, A.R. Srinivasan, S.C. Fahrenkrug, D.A. Largaespada, J. Takeda, K. Horie, W.K. Olson, P.B. Hackett. Target-site preferences of Sleeping Beauty transposons. J. Mol. Biol. 346: 161-173, 2005.

Yusa K., K. Horie, G. Kondoh, M. Kouno, Y. Maeda, T. Kinoshita, and J. Takeda. Genome-wide phenotype analysis in ES cells by regulated disruption of the Bloom’s syndrome gene. Nature 429, 896-899, 2004.

Yusa K., J. Takeda, K. Horie. Enhancement of Sleeping Beauty transposition by CpG methylation: possible role of heterochromatin formation, Mol.Cell.Biol. 24; 4004-4018, 2004.

Silic-Benussi M, I. Cavallari, T. Zorzan, E. Rossi, H. Hiraragi, A. Rosato, K. Horie, D. Saggioro, M.D. Lairmore, L. Willems, L. Chieco-Bianchi, D.M. D’Agostino, V. Ciminale. Suppression of tumor growth and cell proliferation by p13II, a mitochondrial protein of human T-cell leukemia virus type 1. Proc Natl Acad Sci USA 101:6629-6634, 2004.

Kouno M., G. Kondoh, K. Horie, N. Komazawa, N. Ishii, Y.Takahashi, J. Takeda, & T. Hashimoto. Ahnak/Desmoyokin is dispensable for proliferation, differentiation, and maintenance of integrity in mouse epidermis. J. Invest. Dermatol.123: 700-707, 2004.

Takagi S., H. Tojo, S. Tomita, S. Sano, S. Itami, M. Hara, S. Inoue, K. Horie, G. Kondoh, K. Hosokawa, F.J. Gonzalez, J. Takeda. Alteration of the 4-sphingenine scaffolds of ceramides in keratinocyte-specific Arnt deficient mice affects skin barrier function. J. Clin. Invest. 112: 1372-1382, 2003.

Horie K., K. Yusa, K. Yae, J. Odajima, S. E.J. Fischer, V.W. Keng, T. Hayakawa, S. Mizuno, G. Kondoh, T. Ijiri, Y. Matsuda, R.H.A. Plasterk, J. Takeda. Characterization of Sleeping Beauty transposition and its application to genetic screening in mice. Mol.Cell.Biol. 23: 9189-9207, 2003.

von Gegerfelt A.S., V. Liska, P.D. Li, H.M. McClure, K. Horie, F. Nappi, D.C. Montefiori, G.N. Pavlakis, M.L. Marthas, R.M. Ruprecht, B.K. Felber ; Rev-independent SIV strains are non-pathogenic in neonate macaques. J. Virol. 76:96-104, 2002.

Koike H., K. Horie, H. Fukuyama, G. Kondoh, S. Nagata, J. Takeda ; Efficient biallelic mutagenesis with Cre/loxP-mediated inter-chromosomal recombination. EMBO Rep. 3: 433-437, 2002.

Horie K., A. Kuroiwa, M. Ikawa, M. Okabe, G. Kondoh, Y. Matsuda, J. Takeda ; Efficient chromosomal transposition of a Tc1/mariner-like transposon Sleeping Beauty in mice. Proc. Natl. Acad. Sci. USA 98: 9191-9196, 2001.