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Generation and phenotype analysis of zebrafish mutations of obesity-related genes lepr and mc4r

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Author:
No author available
Journal Title:
Acta Physiologica Sinica
Issue:
1
DOI:
10.13294/j.aps.2016.0076
Key Word:
肥胖;斑马鱼;瘦素受体;黑素皮质素受体4;CRISPR/Cas9技术;obesity;zebrafish;lepr;mc4r;CRISPR/Cas9 technology

Abstract: 肥胖已经成为全球性的公共卫生问题,严重影响人类的身体健康和生活品质.本文运用CRISPR/Cas9技术,构建了肥胖相关基因——瘦素受体(leptin receptor,lepr)和黑素皮质素受体4(melanocortin-4 receptor,mc4r)的斑马鱼突变体,并对其进行形态和功能分析.结果显示,lepr+和mc4r+斑马鱼在胚胎和幼鱼期没有明显异常,但在成年期,lepr-/-和mc4r-斑马鱼相比对照进食增多、体重增加、体脂含量升高,呈现肥胖表型.血糖测定结果显示,饱食喂养条件可以诱导lepr和mc4r-/-成年斑马鱼出现糖耐量受损的现象.进一步地,运用real time RT-PCR对76个能量代谢相关基因在lepr+和mc4r-/-斑马鱼肝脏中转录表达水平进行检测,并与Lepob/ob小鼠肝脏cDNA microarray的数据比较,发现胰岛素/胰岛素样生长因子信号转导通路(insulin/IGF signaling pathway,ISS)相关的基因在lepr-斑马鱼和Lepob/ob小鼠肝脏中表达变化具有较高的正相关性,提示肥胖调控网络在进化中维持了一定的功能保守性.

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