KCNH6基因肝脏特异性敲除小鼠的构建及其初步应用

doi:10.3969/j.issn.1006-7795.2020.01.002

首都医科大学学报 ›› 2020, Vol. 41 ›› Issue (1): 8-13.doi: 10.3969/j.issn.1006-7795.2020.01.002

• 糖尿病的临床与基础研究 • 上一篇下一篇

KCNH6基因肝脏特异性敲除小鼠的构建及其初步应用

卢晶, 李奇, 朱晓蓉, 谢荣荣, 杨金奎

首都医科大学附属北京同仁医院内分泌科糖尿病防治研究北京市重点实验室北京市糖尿病研究所, 北京 100730

收稿日期:2019-12-12 出版日期:2020-02-21 发布日期:2020-02-13
通讯作者: 杨金奎 E-mail:jinkui.yang@gmail.com
基金资助:
国家重点研发计划（2017YFC0909600），国家自然科学基金（81800688），首都医科大学附属北京同仁医院科研基金（TRYY-KYJJ-2016-013），北京市属医院科研培育计划（PX2019006）。

Construction and preliminary application of conditional KCNH6-knockout mice

Lu Jing, Li Qi, Zhu Xiaorong, Xie Rongrong, Yang Jinkui

1. Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing Key Laboratory of Diabetes Research and Care, Beijing Diabetes Institute, Beijing 100730, China

Received:2019-12-12 Online:2020-02-21 Published:2020-02-13
Supported by:
This study was supported by National Key P&D Program of China (2017YFC0909600);National Natural Science Foundation of China (81800688); Foundation of Beijing Tongren Hospital,Capital Medical University (TRYY-KYJJ-2016-013);Beijing Municipal Administration of Hospitals Incubating Program (PX2019006).

摘要/Abstract

摘要： 目的构建KCNH6基因肝脏细胞特异性敲除小鼠，并监测其肝脏血脂变化。方法运用Cas9技术构建KCNH6^flox/flox转基因小鼠，将其与肝脏细胞特异性表达Cre重组酶工具鼠（Alb-cre）进行杂交，采用聚合酶链式反应（polymerase chain reaction，PCR）方法鉴定基因型。监测基因敲除小鼠和同窝对照小鼠的体质量和进食量。分别检测8周和20周雌雄各两组小鼠的三酰甘油、胆固醇、高密度脂蛋白胆固醇和低密度脂蛋白胆固醇。结果成功构建KCNH6基因肝脏细胞特异性敲除小鼠，其基因型为KCNH6^flox/flox/Cre^T。与同窝对照组相比，基因敲除小鼠的体质量和进食量均无明显变化。8周雄性和雌性小鼠的血脂无明显变化。20周时雄性小鼠的胆固醇、三酰甘油和低密度脂蛋白胆固醇均有明显升高。结论成功构建了KCNH6基因肝脏细胞特异性敲除小鼠动物模型，成年雄性小鼠存在肝脏血脂代谢异常。动物模型的构建为探讨KCNH6基因在肝脏脂代谢中的作用提供重要研究平台。

关键词: KCNH6, 条件性敲除, 肝脏特异性, Alb-cre, 脂代谢

Abstract: Objective To construct KCNH6 gene specific liver knockout mice and observe the changes of liver lipid metabolism. Methods KCNH6^flox/flox transgenic mice were constructed by Cas9 technique and hybridized with Alb-cre mouse which was specifically expressed Cre in liver cells. The genotype was identified by polymerase chain reaction (PCR). Weight and food intake in knockout mice and wildtype mice were detected. Triglycerides (TG), total cholesterol (TC), high density lipoprotein-cholesterol (HDL-C) and low density lipoprotein-cholesterol (LDL-C) were assessed at 8 and 20 weeks, respectively. Results KCNH6 gene liver cell specific knockout mice were constructed, with the genotype of KCNH6^flox/flox/Cre^T. There were no significant changes in body weight and food intake of the mice in the control group. There was no significant change in lipid metabolism in male and female mice at 8 weeks. Cholesterol levels increased in male mice at 20 weeks. Conclusion The mouse model of KCNH6 gene liver cell specific knockout was constructed. Abnormal lipid metabolism was observed. The establishment of animal model provides a research platform to explore the role of KCNH6 gene in liver lipid metabolism.

Key words: KCNH6, conditional knockout, liver specific, Alb-cre, lipid metabolism

中图分类号:

R587

卢晶, 李奇, 朱晓蓉, 谢荣荣, 杨金奎. KCNH6基因肝脏特异性敲除小鼠的构建及其初步应用[J]. 首都医科大学学报, 2020, 41(1): 8-13.

Lu Jing, Li Qi, Zhu Xiaorong, Xie Rongrong, Yang Jinkui. Construction and preliminary application of conditional KCNH6-knockout mice[J]. Journal of Capital Medical University, 2020, 41(1): 8-13.

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KCNH6基因肝脏特异性敲除小鼠的构建及其初步应用

Construction and preliminary application of conditional KCNH6-knockout mice

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