Hello Shuang Xia

Drug-induced hepatotoxicity is a major safety concern in drug development. Its prediction and prevention have been hindered by limited knowledge of the underlying mechanisms because of a lack of animal models. Different strains of mice used might cause differences in the results and potential mechanistic conclusions. Mouse models are also dependent on genetic background, sex, age, diet and microbiota.

For instance,

In halothane-induced hepatitis mouse model, BALB/c mice were found to be the most susceptible strain whereas there is no significant hepatotoxicity observed in C57BL/6J mice.

C3H/HeJ mice carry a spontaneous mutation in the toll-like receptor4(Tlr4) gene, which makes them less responsive to endotoxin. The C3H/HeJ mice are also less susceptible to acetaminophen(APAP) toxicity than other C3H substrains.

Interestingly, C57Bl/6J mice also carry a spontaneous mutation in the nicotinamide nucleotide transhydrogenase (Nnt) gene that results in loss of its activity. Normally, Nnt maintains high concentrations of NADPH in the mitochondrial matrix, which is important for several reactions including the reduction of glutathione disulfide (GSSG) back to the reduced form. However, under conditions when the mitochondrial electron transport chain is impaired, the enzyme works in the opposite direction, i.e. Nnt functions to generate more NADH for use in the electron transport chain, which leads to reduction of NADPH levels and consequently lower antioxidant capacity in the mitochondria.

I would suggest you try both C57 BL/6J as well as Balb/c, (though C57BL/6J is mostly used) to investigate the hepatotoxicity of sunitinib and compare the results.

Also, please refer to the paper I have attached below. It may be helpful.

Article Animal models of drug-induced liver injury

Best.