Creation and preliminary characterization of a leptin knockout rat.
Creation and preliminary characterization of a leptin knockout rat.
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DOI：
10.1210/en.2012-1462
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发表时间：
2012-09
期刊：
影响因子：
4.8
通讯作者：
S. Vaira;Chang Yang;Aaron M. McCoy;K. Keys;Shurong Xue;E. Weinstein;D. Novack;X. Cui
中科院分区：
文献类型：
--
作者：
S. Vaira;Chang Yang;Aaron M. McCoy;K. Keys;Shurong Xue;E. Weinstein;D. Novack;X. Cui
瘦素是一种主要由脂肪细胞分泌的类胡萝卜素激素，调节以食物摄入和能量消耗为中心的各种途径，包括胰岛素敏感性、生育力、免疫系统和骨代谢。在这里，使用锌指核酸酶技术，我们创造了第一个瘦素敲除大鼠。纯合子瘦素缺失大鼠肥胖，血清胆固醇、甘油三酯和胰岛素水平显著高于野生型对照组。尽管多次尝试，但两种性别都没有产生后代。瘦素基因敲除的大鼠免疫系统也受到抑制。此外，通过瘦素缺失大鼠股骨的显微计算机断层扫描检查显示，与野生型同窝仔相比，股骨的骨小梁骨矿物质密度和骨体积均显著增加。我们的模型应该是有用的许多不同领域的研究，如肥胖，糖尿病和骨代谢相关疾病。
Leptin, a cytokine-like hormone secreted mainly by adipocytes, regulates various pathways centered on food intake and energy expenditure, including insulin sensitivity, fertility, immune system, and bone metabolism. Here, using zinc finger nuclease technology, we created the first leptin knockout rat. Homozygous leptin null rats are obese with significantly higher serum cholesterol, triglyceride, and insulin levels than wild-type controls. Neither gender produced offspring despite of repeated attempts. The leptin knockout rats also have depressed immune system. In addition, examination by microcomputed tomography of the femurs of the leptin null rats shows a significant increase in both trabecular bone mineral density and bone volume of the femur compared with wild-type littermates. Our model should be useful for many different fields of studies, such as obesity, diabetes, and bone metabolism-related illnesses.