Preliminary Characterization of a Leptin Receptor Knockout Rat Created by CRISPR/Cas9 System

被引：39

作者：

Bao, Dan ^{[1
,2
]}

Ma, Yuanwu ^{[1
,2
]}

Zhang, Xu ^{[1
,2
]}

Guan, Feifei ^{[1
,2
]}

Chen, Wei ^{[1
,2
]}

Gao, Kai ^{[1
,2
]}

Qin, Chuan ^{[3
,4
]}

Zhang, Lianfeng ^{[1
,2
]}

机构：

[1] Chinese Acad Med Sci, Key Lab Human Dis Comparat Med, Minist Hlth, Inst Lab Anim Sci, Beijing, Peoples R China

[2] Peking Union Med Coll, Comparat Med Ctr, Beijing, Peoples R China

[3] Chinese Acad Med Sci, Key Lab Human Dis Anim Model, State Adm Tradit Chinese Med, Inst Lab Anim Sci, Beijing, Peoples R China

[4] Peking Union Med Coll, Comparat Med Ctr, Beijing, Peoples R China

来源：

SCIENTIFIC REPORTS | 2015年 / 5卷

关键词：

DIABETIC COMPLICATIONS; FATTY RAT; OBESE; ZUCKER; MUTATION; EXPRESSION; IDENTIFICATION; HYPERGLYCEMIA; PREVENTION; PHENOTYPE;

D O I：

10.1038/srep15942

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Leptin receptor, which is encoded by the diabetes (db) gene and is highly expressed in the choroid plexus, regulatesenergy homeostasis, the balance between food intake and energy expenditure, fertility and bone mass. Here, using CRISPR/Cas9 technology, we created the leptin receptor knockout rat. Homozygous leptin receptor null rats are characterized by obesity, hyperphagia, hyperglycemia, glucose intolerance, hyperinsulinemia and dyslipidemia. Due to long-term poor glycemic control, the leptin receptor knockout rats also develop some diabetic complications such as pancreatic, hepatic and renal lesions. In addition, the leptin receptor knockout rats show a significant decrease in bone volume and bone mineral density of the femur compared with their wildtype littermates. Our model has rescued some deficiency of the existing rodent models, such as the transient hyperglycemia of db/db mice in the C57BL/6J genetic background and the delayed onset of glucose intolerance in the Zucker rats, and it is proven to be a useful animal model for biomedical and pharmacological research on obesity and diabetes.

引用

页数：10

共 38 条

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