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使用CRISPR-Cas9进行DNAJB3的遗传删除,产生了不一致的表型

Shadi Nejat¹, Kalhara R Menikdiwela¹, Aliyah Efotte¹

¹Department of Nutritional Sciences & Obesity Research Institute, Texas Tech University, Lubbock, TX 79409, USA.

|October 28, 2023

概括

在小鼠中,DNAJB3 缺乏会加剧饮食引起的肥胖和胰岛素抵抗. 丢失DNAJB3会损害葡萄糖代谢并增加炎症,突出其对代谢疾病的保护作用.

科学领域:

代谢研究研究代谢研究
分子生物学分子生物学
遗传学遗传学是一个

背景情况:

肥胖和2型糖尿病 (T2D) 涉及失调的基因,包括DNAJB3,它在肥胖中表达受损,并与代谢压力有关.
以前的研究表明,DNAJB3对肥胖和T2D起着保护作用,但根本机制尚不清楚.

研究的目的:

用饮食诱导的肥胖和胰岛素抵抗的小鼠模型来验证人类实验对象的发现.
阐明DNAJB3影响新陈代谢健康和葡萄糖平衡的机制.

主要方法:

使用CRISPR-Cas9.9生成了三条DNAJB3淘汰赛 (KO) 鼠标线.
养KO和野生型 (WT) littermates 16 周的高脂肪 (HF) 饮食,监测体重,组成,耐葡萄糖和胰岛素敏感性.
分析了白色脂肪组织 (WAT) 和骨肌肉,以检测炎症标记物,葡萄糖转运体和内质网膜 (ER) 压力标记物的基因表达.

主要成果:

与WT小鼠相比,DNAJB3 KO 47小鼠的体重和脂肪量增加.
KO 47小鼠表现出葡萄糖耐受性受损,与WAT中GLUT4基因表达的降低有关.
KO 47小鼠在男性的WAT和ER压力标志物 (BiP/Grp78) 中表现出高的促炎标志物 (TNF-α),与人类的观察结果一致.

结论:

DNAJB3 KO 47小鼠模型复制了与肥胖和胰岛素抵抗相关的人类代谢表型.
DNAJB3在调节新陈代谢功能和葡萄糖平衡中发挥着重要作用.
进一步研究DNAJB3的机制和治疗肥胖和T2D的治疗潜力是有必要的.

关键词:

克里斯普尔-Cas9是什么意思 DNAJB3 DNAJB3 的意思压力ERER压力ERER压力脂肪组织的脂肪组织.葡萄糖的恒常性是葡萄糖的恒常性.热冲击蛋白质是一种热冲击蛋白质.这是一种炎症炎症炎症炎症.胰岛素耐药性是一种胰岛素耐药性.肥胖肥胖肥胖肥胖肥胖肥胖肥胖肥胖 2 型糖尿病 2 型糖尿病

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