Abstract 13545: MicroRNA-33b Knock-in Mice for an Intron of Sterol Regulatory Element-Binding Factor 1 (Srebf1) Exhibit Reduced HDL-C in vivo
Abstract 13545: MicroRNA-33b Knock-in Mice for an Intron of Sterol Regulatory Element-Binding Factor 1 (Srebf1) Exhibit Reduced HDL-C in vivo
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发表时间：
2014-11
期刊：
影响因子：
37.8
通讯作者：
Takahiro Horie;Tomohiro Nishino;Osamu Baba;Y. Kuwabara;T. Nakao;M. Nishiga;S. Usami;M. Izuhara;Fumiko Nakazeki;Y. Ide;S. Koyama;M. Yokode;T. Kita;Takeshi Kimura;K. Ono
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文献类型：
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作者：
Takahiro Horie;Tomohiro Nishino;Osamu Baba;Y. Kuwabara;T. Nakao;M. Nishiga;S. Usami;M. Izuhara;Fumiko Nakazeki;Y. Ide;S. Koyama;M. Yokode;T. Kita;Takeshi Kimura;K. Ono
背景：微小RNA（microRNAs，miRs）是一类非蛋白质编码的小分子RNA，能与特定的mRNA结合，抑制mRNA的翻译或促进mRNA的降解。最近的研究表明，位于固醇调节元件结合蛋白（SREBP）2内含子内的miR-33（miR-33 a）控制胆固醇稳态，可能是治疗动脉粥样硬化的一个可能的治疗靶点。灵长类动物（而非啮齿类动物）表达来自SREBF 1内含子的第二个miR-33基因（miR-33 b）。为了解决miR-33 b在体内的功能，我们开发了人源化小鼠，其中miR-33 b转基因插入Srebf 1内含子内。方法和结果：由于miR-33 b位于人SREBF 1的第16内含子，且人和小鼠之间在第16和17外显子有很高的同源性，因此通过常规的基因打靶方法将人miR-33 b序列导入小鼠SREBF 1的第16内含子。我们成功建立了具有C57 BL/6背景的miR-33 b基因敲入（KI）小鼠，这种miR-33 b KI策略没有改变Srebf 1内含子16的表达。
Background: MicroRNAs (miRs) are small non-protein-coding RNAs that bind to specific mRNAs and inhibit translation or promote mRNA degradation. Recent reports, including ours, indicated that miR-33 (miR-33a) located within the intron of sterol regulatory element-binding protein (SREBP) 2 controls cholesterol homeostasis and can be a possible therapeutic target for treating atherosclerosis. Primates, but not rodents, express a second miR-33 gene (miR-33b) from an intron of SREBF1. To address miR-33b function in vivo, we developed humanized mice, in which a miR-33b transgene is inserted within a Srebf1 intron. Methods and Results: The human miR-33b sequence was introduced into intron 16 of mouse Srebf1 by conventional gene targeting methods, because miR-33b is located in intron 16 of human SREBF1 and there are high homologies in exons 16 and 17 between human and mouse. We successfully established miR-33b knock-in (KI) mice with C57BL/6 background and this miR-33b KI strategy did not alter Srebf1 intron 16 s...