Generation of obese rat model by transcription activator-like effector nucleases targeting the leptin receptor gene
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Published:2016-05-25
Issue:2
Volume:60
Page:152-157
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ISSN:1674-7305
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Container-title:Science China Life Sciences
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language:en
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Short-container-title:Sci. China Life Sci.
Author:
Chen Yuting,Lu Wenqing,Gao Na,Long Yi,Shao Yanjiao,Liu Meizhen,Chen Huaqing,Ye Shixin,Ma Xueyun,Liu Mingyao,Li Dali
Abstract
Abstract
The laboratory rat is a valuable mammalian model organism for basic research and drug discovery. Here we demonstrate an efficient methodology by applying transcription activator-like effector nucleases (TALENs) technology to generate Leptin receptor (Lepr) knockout rats on the Sprague Dawley (SD) genetic background. Through direct injection of in vitro transcribed mRNA of TALEN pairs into SD rat zygotes, somatic mutations were induced in two of three resulting pups. One of the founders carrying bi-allelic mutation exhibited early onset of obesity and infertility. The other founder carried a chimeric mutation which was efficiently transmitted to the progenies. Through phenotyping of the resulting three lines of rats bearing distinct mutations in the Lepr locus, we found that the strains with a frame-shifted or premature stop codon mutation led to obesity and metabolic disorders. However, no obvious defect was observed in a strain with an in-frame 57 bp deletion in the extracellular domain of Lepr. This suggests the deleted amino acids do not significantly affect Lepr structure and function. This is the first report of generating the Lepr mutant obese rat model in SD strain through a reverse genetic approach. This suggests that TALEN is an efficient and powerful gene editing technology for the generation of disease models.
Publisher
Springer Science and Business Media LLC
Subject
General Agricultural and Biological Sciences,General Environmental Science,General Biochemistry, Genetics and Molecular Biology
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