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学科主题: 基础医学
题名:
Establishment of liver specific glucokinase gene knockout mice: a new animal model for screening anti-diabetic drugs
作者: Zhang, YL; Tan, XH; Xiao, MF; Li, H; Mao, YQ; Yang, X; Tan, HR
关键词: animal disease model ; non insulin dependent diabetes mellitus ; type 2 diabetes mellitus ; glucokinase ; knockout mice
刊名: ACTA PHARMACOLOGICA SINICA
发表日期: 2004-12-01
卷: 25, 期:12, 页:1659-1665
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Chemistry, Multidisciplinary ; Pharmacology & Pharmacy
研究领域[WOS]: Chemistry ; Pharmacology & Pharmacy
关键词[WOS]: DIABETES-MELLITUS ; CRE RECOMBINASE ; MOUSE MODEL ; MUTATIONS ; RATS ; ABNORMALITIES ; HYPERGLYCEMIA ; RECEPTOR ; STRAIN ; CELLS
英文摘要:

AIM: To characterize the liver-specific role of glucokinase in maintaining glucose homeostasis and to create an animal model for diabetes. METHODS: We performed hepatocyte-specific gene knockout of glucokinase in mice using Cre-loxP gene targeting strategy. First, two directly repeated loxP sequences were inserted to flank the exon 9 and exon 10 of glucokinase in genomic DNA. To achieve this, linearized targeting vector was electroporated into ES cells. Then G418- and Gancyclovir-double-resistant clones were picked and screened by PCR analysis and the positives identified by PCR were confirmed by Southern blot. A targeted clone was selected for microinjection into C57BL/6J blastocysts and implanted into pseudopregnant FVB recipient. Chimeric mice and their offspring were analyzed by Southern blot. Then by intercrossing the Alb-Cre transgenic mice with mice containing a conditional gk allele, we obtained mice with liver-specific glucokinase gene knockout. RESULTS: Among 161 double resistant clones 4 were positive to PCR and Southern blot and only one was used for further experiments. Eventually we generated the liver specific glucokinase knockout mice. These mice showed increased glucose level with age and at the age of 6 weeks fasting blood glucose level was significantly higher than control and they also displayed impaired glucose tolerance. CONCLUSION: Our studies indicate that hepatic glucokinase plays an important role in glucose homeostasis and its deficiencies contribute to the development of diabetes. The liver glucokinase knockout mouse is an ideal animal model for MODY2, and it also can be applied for screening anti-diabetic drugs.

语种: 英语
WOS记录号: WOS:000225845200014
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/67872
Appears in Collections:基础医学院_药理学系_期刊论文

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作者单位: 1.Peking Univ, Sch Basic Med Sci, Hlth Sci Ctr, Dept Pharmacol, Beijing 100083, Peoples R China
2.Acad Mil Med Sci, Inst Biotechnol, Beijing 100071, Peoples R China

Recommended Citation:
Zhang, YL,Tan, XH,Xiao, MF,et al. Establishment of liver specific glucokinase gene knockout mice: a new animal model for screening anti-diabetic drugs[J]. ACTA PHARMACOLOGICA SINICA,2004,25(12):1659-1665.
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