RGD Reference Report - Generation of obese rat model by transcription activator-like effector nucleases targeting the leptin receptor gene. - Rat Genome Database

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Generation of obese rat model by transcription activator-like effector nucleases targeting the leptin receptor gene.

Authors: Chen, Yuting  Lu, Wenqing  Gao, Na  Long, Yi  Shao, Yanjiao  Liu, Meizhen  Chen, Huaqing  Ye, Shixin  Ma, Xueyun  Liu, Mingyao  Li, Dali 
Citation: Chen Y, etal., Sci China Life Sci. 2017 Feb;60(2):152-157. doi: 10.1007/s11427-016-5049-y. Epub 2016 May 25.
RGD ID: 12910507
Pubmed: PMID:27225180   (View Abstract at PubMed)
DOI: DOI:10.1007/s11427-016-5049-y   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
obesity  ISOLepr (Rattus norvegicus)12910507; 12910507 RGD 
obesity  IMP 12910507; 12910507; 12910507; 12910507; 12910507 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Lepr  (leptin receptor)
Leprem2  (leptin receptor; TALEN induced mutant 2)
Leprem3  (leptin receptor; TALEN induced mutant 3)

Genes (Mus musculus)
Lepr  (leptin receptor)

Genes (Homo sapiens)
LEPR  (leptin receptor)

SD-Leprem2  (NA)
SD-Leprem3  (NA)

Objects referenced in this article
Gene Leprem1 leptin receptor; TALEN induced mutant 1 Rattus norvegicus
Strain SD-Leprem1 null Rattus norvegicus

Additional Information