葛常辉王玉华杨晓明

【摘要】目的

探讨Notch1信号传递对小鼠脂肪代谢以及血糖水平的影响。方法Notch1基因点突变小鼠能导致信号传递减少，但能正常存活。应用RT-PCR和Western Blot等方法分析了点突变对Notch1信号传递能力的影响。应用核磁共振分析了小鼠体内组成脂肪的含量，并应用葡萄糖分析仪检测了血糖的变化。结果点突变导致Notch1信号传递能力降低，靶基因表达下降，突变组小鼠在成年后体重低于对照组。突变组小鼠的腹部肠系膜、腹股沟以及背部等处的脂肪均明显减少。全身组分分析结果显示脂肪比例减少，而瘦体重增加。血糖分析则表明突变小鼠血液中的葡萄糖水平降低。结论Notch1信号传递系统可能参与血糖调节和小鼠体内脂肪组织的发育与代谢，进而影响脂肪的含量。

【关键词】Notch1信号传递;脂肪;血糖

doi:10.3969/j.issn.1006-6187.2011.05.016

Effects of Notch1 mutation on mouse fatty metabolism and blood sugar

GE Chang-hui, WANG Yu-hua, YANG Xiao-ming. Key Lab of Biochemistry and Molecular Biology, Beijing Insititute of Radiation Medicine, Beijing 100850, China

【Abstract】ObjectiveTo investigate the effects of Notch1 mutation on mouse fatty metabolism and blood sugar and the relative mechamism.MethodsThe knock-in mice with a Notch1 point mutation can survive, but show a reduced Notch1 signaling. RT-PCR and Western blot were used to analyze effects of Notch1 mutation on signaling transduction. NMR (nuclear magnetic resonance) was used to analyze mouse whole body fat composition.ResultsNotch1 point mutation decreased Notch1 signaling level and decreased target genes expression. The body weight of mutant mice was lower than that of normal control after growing up. The testis fat, mesenteric fat and para-kidney fat were obviously reduced. Whole body composition analysis showed that fatty mass was reduced, but lean mass was increased. Blood glucose was reduced in mutant mice, too.ConclusionsNotch1 signaling pathway may involve the regulation of blood sugar and fat development and metabolism.

【Key words】Notch1 signaling transduction;Fat;Blood glucose