The 14th Ile residue is essential for Leptin function in regulating energy homeostasis in rat
In: Scientific Reports, Jg. 6 (2016-07-01)
Online
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Zugriff:
LEPTIN (LEP) is a circulating hormone released primarily from white adipocytes and is crucial for regulating satiety and energy homeostasis in humans and animals. Using the CRISPR technology, we created a set of Lep mutant rats that carry either null mutations or a deletion of the 14th Ile (LEP∆I14) in the mature LEP protein. We examined the potential off-target sites (OTS) by whole-genome high-throughput sequencing and/or Sanger-sequencing analysis and found no OTS in mutant rats. Mature LEP∆I14 is incessantly produced and released to blood at a much elevated level due to the feedback loop. Structure modeling of binding conformation between mutant LEP∆I14 and LEPTIN receptor (LEPR) suggests that the conformation of LEP∆I14 impairs its binding with LEPR, consistent with its inability to activate STAT3-binding element in the luciferase reporter assay. Phenotypic study demonstrated that Lep∆I14 rats recapitulate phenotypes of Lep-null mutant rats including obesity, hyperinsulinemia, hepatic steatosis, nephropathy and infertility. Compared to the existing ob/ob mouse models, this Lep∆I14/∆I14 rat strain provides a robust tool for further dissecting the roles of LEP in the diabetes related kidney disease and reproduction problem, beyond its well established function in regulating energy homeostasis.
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The 14th Ile residue is essential for Leptin function in regulating energy homeostasis in rat
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Autor/in / Beteiligte Person: | Ding, Guohui ; Lu, Lina ; Li, Hong ; Li, Yixue ; Hu, Youtian ; Xue, Zhigang ; Liu, Tiancheng ; Chen, Jiayu ; Hu, Youjin ; Gao, Shaorong ; Zhou, Jinping ; Wang, Zhen ; Fan, Guoping ; Zhu, Xianmin ; Du, Guizhen ; He, Di ; Feng, Yun ; Wu, Fang ; Xu, Shuyang |
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Zeitschrift: | Scientific Reports, Jg. 6 (2016-07-01) |
Veröffentlichung: | Nature Publishing Group, 2016 |
Medientyp: | unknown |
ISSN: | 2045-2322 (print) |
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