ウツギサワ　タイジユ   UTSUGISAWA Taijiyu   槍澤　大樹    所属   医学部 医学科（東京女子医科大学病院）    職種   准教授
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Development of cellular models for ribosomal protein S19 (RPS19)-deficient diamond-blackfan anemia using inducible expression of siRNA against RPS19.
掲載誌名	正式名：Molecular therapy : the journal of the American Society of Gene Therapy 略　 称：Mol Ther ISSNコード：15250016/15250016
掲載区分	国外
巻・号・頁	11(4),pp.627-630
著者・共著者	Miyake Koichi, Flygare Johan, Kiefer Thomas, Utsugisawa Taiju, Richter Johan, Ma Zhi, Wiznerowicz Maciej, Trono Didier, Karlsson Stefan
発行年月	2005/04
概要	Diamond-Blackfan anemia (DBA) is a congenital red cell aplasia in which 25% of the patients have a mutation in the ribosomal protein S19 (RPS19) gene. No models exist for RPS19-deficient DBA and the molecular pathogenesis is unknown. To establish an in vitro inducible model for DBA, human erythroid leukemic cell lines, TF-1 and UT-7 cells, were cotransduced with a lentiviral vector expressing the green fluorescent protein (GFP) gene and small interfering RNA (siRNA) against RPS19 controlled by a tet operator regulatory element and another transactivator vector containing the red fluorescent protein (RFP) gene and the cDNA encoding a tetracycline-controllable transcriptional repressor. Following transduction, the RFP-positive and GFP-negative cell population was sorted by flow cytometry. Upon incubation with doxycycline (0.5 mug/ml), more than 98% of cells expressed GFP and the siRNA. Significant suppression of erythroid differentiation, cell growth, and colony formation was observed in cells treated with siRNA against RPS19 but not in cells treated with a control vector. These findings show that RPS19 plays an important role in the regulation of hematopoietic cell proliferation and erythroid differentiation. These novel cell lines represent models for RPS19-deficient DBA and can be used to identify the molecular mechanisms in RPS19-deficient DBA.
DOI	10.1016/j.ymthe.2004.12.001
PMID	15771965