RenaSci offers the choline deficient (CD) diet mouse model of NASH and fibrosis. This model was developed as a refinement of the methionine and choline deficient (MCD) diet mouse. The MCD mouse has the disadvantage of inducing ~40% weight loss over 6 weeks. This is in contrast to the ~15% reduction in body weight observed in the CD mouse.

 

Mice are maintained on the CD diet for 6 weeks. Resulting in increases in the following parameters:

• Plasma levels of liver enzymes (ALT and AST)
• Liver lipids
• Histological endpoints of NASH (i.e. steatosis, hepatocellular ballooning and lobular inflammation) overall NAS and  fibrosis scores

 

RenaSci’s CD mouse has been validated with the peroxisome proliferator activated receptor (PPAR) gamma agonist, pioglitazone, and the dual PPAR alpha/delta agonist, elafibranor. These drugs have efficacy in the clinic to improve NASH and have reduced or inhibited many of the features of NASH and fibrosis in the CD mouse.

 

These results demonstrate that RenaSci’s CD mouse can be used as a simple, short-term (6 weeks) model to identify compounds with potential for the treatment of NASH and fibrosis.

Effects of pioglitazone & elafibranor on liver
pathology in mice on a CD diet

Mean and SEM (n=11-13). Significance vs normal diet control are denoted by **p<0.01 and ***p<0.001. Significance vs CD diet control are denoted by †p<0.05, ††p<0.01 and †††p<0.001.
* The NAFLD activity score (NAS) generated by combining scores for # parameters; steatosis, hepatocellular ballooning and lobular inflammation.

 

Effects of pioglitazone & elafibranor on liver
triglycerides in mice on a CD diet

Liver triglycerides

 

Sirius red stained liver

 

Representative images of sirius red stained liver sections, magnification x10 demonstrating the difference between
the vehicle, CD diet, Pioglitazone 15 mg/kg po bid and Elafibranor 30/20 mg/kg po qd groups.

 

 

 

CD mouse exhibits a ~15% weight loss

This graph demonstrates body weight against time for the vehicle, CD diet, Pioglitazone 15 mg/kg po bid and Elafibranor 30/20 mg/kg po qd groups.

 

 

Get in touch to learn more about RenaSci’s CD mouse model of NASH and fibrosis.

 

Explore our other models of NASH