RGD Reference Report - Generation of TALEN-mediated FH knockout rat model. - Rat Genome Database

Send us a Message



 Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes Community Projects (beta) QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap)  (beta) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer)
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease Coronavirus Disease Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models   new Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes GERRC (Gene Editing Rat Resource Center) Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Presentations Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources

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.
RGD ID: 13792708
Pubmed: PMID:27556703   (View Abstract at PubMed)
PMCID: PMC5308680   (View Article at PubMed Central)
DOI: DOI:10.18632/oncotarget.11429   (Journal Full-text)

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.



Phenotype Annotations    

Phenotype Values via PhenoMiner     Click to see Annotation Detail View
Options:  View chart  |  Download data table  |  View expanded data table  |  Show All Strains Clinical Measurement

Strains with Phenominer Data Strains with phenominer data
SD-Fhem1+/+ SD-Fhem1+/-

Objects Annotated

Genes (Rattus norvegicus)
Fh  (fumarate hydratase)
Fhem1  (fumarate hydratase; TALEN induced mutant 1)

Strains
SD-Fhem1+/-  (NA)

Objects referenced in this article
Strain SD-Fhem1+/+ null Rattus norvegicus

Additional Information