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Generation of TALEN-mediated FH knockout rat model.

Authors: Yu, Dandan  Zhong, Yali  Li, Xiaoran  Li, Yaqing  Li, Xiaoli  Cao, Jing  Fan, Zhirui  Fan, Huijie  Yuan, Long  Xu, Benling  Yuan, Yuan  Zhang, Hongquan  Ji, Zhenyu  Wen, Jian-Guo  Zhang, Mingzhi  Nesland, Jahn M  Suo, Zhenhe 
Citation: Yu D, etal., Oncotarget. 2016 Sep 20;7(38):61656-61669. doi: 10.18632/oncotarget.11429.
Pubmed: (View Article at PubMed) PMID:27556703
DOI: Full-text: DOI:10.18632/oncotarget.11429

Transcription activator-like effector nucleases (TALENs) are valuable tools for precise genome engineering of laboratory animals. Here we utilized this technique for efficient site-specific gene modification to create a fumarate hydratase (FH) gene knockout rat model, in which there was an 11 base-pair deletion in the first exon of the FH gene in 111 rats. 18 live-born targeted mutation offsprings were produced from 80 injected zygotes with 22.5% efficiency, indicating high TALEN knockout success in rat zygots. Only heterozygous deletion was observed in the offsprings. Sixteen pairs of heterozygous FH knockout (FH+/-) rats were arranged for mating experiments for six months without any homozygous KO rat identified. Sequencing from the pregnant rats embryo samples showed no homozygous FH KO, indicating that homozygous FH KO is embryonically lethal. Comparatively, the litter size was decreased in both male and female FH+/- KO rats. There was no behaviour difference between the FH+/- KO and the control rats except that the FH+/- KO male rats showed significantly higher body weight in the 16-week observation period. Clinical haematology and biochemical examinations showed hematopoietic and kidney dysfunction in the FH+/- KO rats. Small foci of anaplastic lesions of tubular epithelial cells around glomeruli were identified in the FH+/- kidney, and these anaplastic cells were comparatively positive for Ki67, p53 and Sox9, and such findings are most probably related to the kidney dysfunction reflected by the biochemical examinations of the rats. In conclusion, we have successfully established an FH+/- KO rat model, which will be useful for further functional FH studies.


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CRRD Object Information
CRRD ID: 13792708
Created: 2018-09-21
Species: All species
Last Modified: 2018-09-21
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.