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Molecular and Cellular Biology, December 2005, p. 10965-10978, Vol. 25, No. 24
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.24.10965-10978.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Disruption of Sept6, a Fusion Partner Gene of MLL, Does Not Affect Ontogeny, Leukemogenesis Induced by MLL-SEPT6, or Phenotype Induced by the Loss of Sept4

Ryoichi Ono,¹ Masafumi Ihara,² Hideaki Nakajima,³ Katsutoshi Ozaki,^1, Yuki Kataoka-Fujiwara,^4, Tomohiko Taki,⁵ Koh-ichi Nagata,^6,¶ Masaki Inagaki,⁶ Nobuaki Yoshida,⁴ Toshio Kitamura,⁷ Yasuhide Hayashi,⁸ Makoto Kinoshita,^2,9 and Tetsuya Nosaka^1*

Division of Hematopoietic Factors,¹ Center of Excellence,³ Laboratory of Gene Expression and Regulation, Center for Experimental Medicine,⁴ Division of Cellular Therapy, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan,⁷ Biochemistry and Cell Biology Unit, HMRO, Kyoto University Graduate School of Medicine, Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan,² Department of Molecular Laboratory Medicine, Kyoto Prefectural University of Medicine Graduate School of Medical Science, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan,⁵ Divisions of Biochemistry and Virology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan,⁶ Gunma Children's Medical Center, 779 Shimohakoda, Kitatachibana, Gunma 377-8577, Japan,⁸ Japan Science and Technology Agency, Kawaguchi Center Building, 4-1-8, Honcho, Kawaguchi-shi, Saitama 332-0012, Japan⁹

Received 23 June 2005/ Returned for modification 27 July 2005/ Accepted 30 September 2005

Septins are evolutionarily conserved GTP-binding proteins that can heteropolymerize into filaments. Recent studies have revealed that septins are involved in not only diverse normal cellular processes but also the pathogenesis of various diseases, including cancer. SEPT6 is ubiquitously expressed in tissues and one of the fusion partner genes of MLL in the 11q23 translocations implicated in acute leukemia. However, the roles of this septin in vivo remain elusive. We have developed Sept6-deficient mice that exhibited neither gross abnormalities, changes in cytokinesis, nor spontaneous malignancy. Sept6 deficiency did not cause any quantitative changes in any of the septins evaluated in this study, nor did it cause any additional changes in the Sept4-deficient mice. Even the depletion of Sept11, a close homolog of Sept6, did not affect the Sept6-null cells in vitro, thus implying a high degree of redundancy in the septin system. Furthermore, a loss of Sept6 did not alter the phenotype of myeloproliferative disease induced by MLL-SEPT6, thus suggesting that Sept6 does not function as a tumor suppressor. To our knowledge, this is the first report demonstrating that a disruption of the translocation partner gene of MLL in 11q23 translocation does not contribute to leukemogenesis by the MLL fusion gene.

Present address: Division of Hematology, Department of Medicine, Jichi Medical School, 3311-1 Yakushiji, Minamikawachi-machi, Kawachi-gun, Tochigi 329-0498, Japan.

Present address: Department of Host Defense, Research Institute for Microbial Disease, Osaka University, Suita, Osaka 565-0871, Japan.

^¶ Present address: Department of Molecular Neurobiology, Institute for Developmental Research, Aichi Human Service Center, 713-8 Kamiya-cho, Kasugai 480-0392, Japan.