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

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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.
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    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
FhRatabnormal kidney morphology  IMP  RGD 
Fhem1Ratabnormal kidney morphology  IMP  RGD 
SD-Fhem1+/-Ratabnormal kidney morphology  IMP  RGD 
FhRatabnormal lymphocyte morphology  IMP  RGD 
Fhem1Ratabnormal lymphocyte morphology  IMP  RGD 
SD-Fhem1+/-Ratabnormal lymphocyte morphology  IMP  RGD 
FhRatdecreased blood uric acid level  IMP  RGD 
Fhem1Ratdecreased blood uric acid level  IMP  RGD 
SD-Fhem1+/-Ratdecreased blood uric acid level  IMP  RGD 
FhRatdecreased eosinophil cell number  IMP  RGD 
Fhem1Ratdecreased eosinophil cell number  IMP  RGD 
SD-Fhem1+/-Ratdecreased eosinophil cell number  IMP  RGD 
FhRatdecreased hematocrit  IMP  RGD 
Fhem1Ratdecreased hematocrit  IMP  RGD 
SD-Fhem1+/-Ratdecreased hematocrit  IMP  RGD 
FhRatdecreased leukocyte cell number  IMP  RGD 
Fhem1Ratdecreased leukocyte cell number  IMP  RGD 
SD-Fhem1+/-Ratdecreased leukocyte cell number  IMP  RGD 
FhRatdecreased litter size  IMP  RGD 
Fhem1Ratdecreased litter size  IMP  RGD 
SD-Fhem1+/-Ratdecreased litter size  IMP  RGD 
FhRatdecreased lymphocyte cell number  IMP  RGD 
Fhem1Ratdecreased lymphocyte cell number  IMP  RGD 
SD-Fhem1+/-Ratdecreased lymphocyte cell number  IMP  RGD 
FhRatdecreased monocyte cell number  IMP  RGD 
Fhem1Ratdecreased monocyte cell number  IMP  RGD 
SD-Fhem1+/-Ratdecreased monocyte cell number  IMP  RGD 
FhRatembryonic lethality  IMP  RGD 
Fhem1Ratembryonic lethality  IMP  RGD 
FhRatincreased blood urea nitrogen level  IMP  RGD 
Fhem1Ratincreased blood urea nitrogen level  IMP  RGD 
SD-Fhem1+/-Ratincreased blood urea nitrogen level  IMP  RGD 
FhRatincreased body weight  IMP male onlyRGD 
Fhem1Ratincreased body weight  IMP male onlyRGD 
SD-Fhem1+/-Ratincreased body weight  IMP male onlyRGD 
FhRatincreased circulating creatinine level  IMP  RGD 
Fhem1Ratincreased circulating creatinine level  IMP  RGD 
SD-Fhem1+/-Ratincreased circulating creatinine level  IMP  RGD 

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