RGD Reference Report - Generation and Characterization of a CYP2C11-Null Rat Model by Using the CRISPR/Cas9 Method. - Rat Genome Database

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Generation and Characterization of a CYP2C11-Null Rat Model by Using the CRISPR/Cas9 Method.

Authors: Wei, Yuan  Yang, Li  Zhang, Xiaoyan  Sui, Danjuan  Wang, Changsuo  Wang, Kai  Shan, Mangting  Guo, Dayong  Wang, Hongyu 
Citation: Wei Y, etal., Drug Metab Dispos. 2018 May;46(5):525-531. doi: 10.1124/dmd.117.078444. Epub 2018 Feb 14.
RGD ID: 150429710
Pubmed: PMID:29444903   (View Abstract at PubMed)
DOI: DOI:10.1124/dmd.117.078444   (Journal Full-text)

CYP2C11 is involved in the metabolism of many drugs in rats. To assess the roles of CYP2C11 in physiology and drug metabolism, a CYP2C11-null rat model was generated using the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9method. A 2-base pair insertion was added to exon 6 of CYP2C11 in Sprague-Dawley rats. CYP2C11 was not detected by western blotting in liver microsomes of CYP2C11-null rats. No off-target effects were found at 11 predicted sites of the knockout model. The CYP2C11-null rats were viable and had no obvious abnormalities, with the exception of reduced fertility. Puberty in CYP2C11-null rats appeared to be delayed by ∼20 days, and the average litter size fell by 43%. Tolbutamide was used as a probe in this drug metabolism study. In the liver microsomes of CYP2C11-null rats, the Vmax and intrinsicclearance values decreased by 22% and 47%, respectively, compared with those of wild-type rats. The Km values increased by 47% compared with that of wild types. However, our pharmacokinetics study showed no major differences in any parameters between the two strains, in both males and females. In conclusion, a CYP2C11-null rat model was successfully generated and is a valuable tool to study the in vivo function of CYP2C11.



Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Cyp2c11Ratabnormal xenobiotic pharmacokinetics sexual_dimorphism IAGPtolbutamidecompared between male and femaleRGD 
Cyp2c11Ratabnormal xenobiotic pharmacokinetics  IMPtolbutamidecompared to wild typeRGD 
Cyp2c11em1NjuRatabnormal xenobiotic pharmacokinetics  IMPtolbutamidecompared to wild typeRGD 
Cyp2c11em1NjuRatabnormal xenobiotic pharmacokinetics sexual_dimorphism IAGPtolbutamidecompared between male and femaleRGD 
SD-Cyp2c11em1NjuRatabnormal xenobiotic pharmacokinetics sexual_dimorphism IAGPtolbutamidecompared between male and femaleRGD 
SD-Cyp2c11em1NjuRatabnormal xenobiotic pharmacokinetics  IMPtolbutamidecompared to wild typeRGD 
Cyp2c11Ratdecreased litter size  IMP compared to wild typeRGD 
Cyp2c11em1NjuRatdecreased litter size  IMP compared to wild typeRGD 
SD-Cyp2c11em1NjuRatdecreased litter size  IMP compared to wild typeRGD 
Cyp2c11Ratdelayed fertility  IMP compared to wild typeRGD 
Cyp2c11em1NjuRatdelayed fertility  IMP compared to wild typeRGD 
SD-Cyp2c11em1NjuRatdelayed fertility  IMP compared to wild typeRGD 
Objects Annotated

Genes (Rattus norvegicus)
Cyp2c11  (cytochrome P450, subfamily 2, polypeptide 11)
Cyp2c11em1Nju  (cytochrome P450, subfamily 2, polypeptide 11; CRISPR/Cas9 induced mutant 1, Nju)

Strains
SD-Cyp2c11em1Nju  (NA)


Additional Information