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    

Mammalian Phenotype
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