Bordone Laura, Cohen Dena, Robinson Ashley, Motta Maria Carla, van Veen Ed, Czopik Agnieszka, Steele Andrew D, Crowe Hayley, Marmor Stephen, Luo Jianyuan, Gu Wei, Guarente Leonard
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Aging Cell. 2007 Dec;6(6):759-67. doi: 10.1111/j.1474-9726.2007.00335.x. Epub 2007 Sep 17.
We generated mice that overexpress the sirtuin, SIRT1. Transgenic mice have been generated by knocking in SIRT1 cDNA into the beta-actin locus. Mice that are hemizygous for this transgene express normal levels of beta-actin and higher levels of SIRT1 protein in several tissues. Transgenic mice display some phenotypes similar to mice on a calorie-restricted diet: they are leaner than littermate controls; are more metabolically active; display reductions in blood cholesterol, adipokines, insulin and fasted glucose; and are more glucose tolerant. Furthermore, transgenic mice perform better on a rotarod challenge and also show a delay in reproduction. Our findings suggest that increased expression of SIRT1 in mice elicits beneficial phenotypes that may be relevant to human health and longevity.
我们培育出了过表达沉默调节蛋白SIRT1的小鼠。通过将SIRT1 cDNA敲入β-肌动蛋白基因座，已培育出转基因小鼠。对于该转基因半合子的小鼠，在多个组织中β-肌动蛋白表达水平正常，而SIRT1蛋白水平较高。转基因小鼠表现出一些与限食小鼠相似的表型：它们比同窝对照小鼠更瘦；代谢更活跃；血液中胆固醇、脂肪因子、胰岛素和空腹血糖水平降低；且对葡萄糖的耐受性更强。此外，转基因小鼠在转棒试验中表现更好，并且繁殖延迟。我们的研究结果表明，小鼠中SIRT1表达增加会引发有益的表型，这可能与人类健康和长寿相关。
