Comparing liver RNA-seq analysis of human, rhesus monkey, mouse and rat

Background

Animal models are commonly utilized by the pharmaceutical industry to evaluate new drugs; however, the results of these studies are not always applicable to humans due to differences between the genetic backgrounds.

Methods

Since liver plays a prominent role in drug metabolism, we evaluated the expression profiles of human, mouse, rat, and rhesus monkey liver tissues. The differentially expressed genes were identified in different genders, strains, and species.

Results

The primates had fewer differences compared to the rodents, suggesting rhesus monkey could be a preferred model organism. Although the human HGFR (MET), a putative AAV3 receptor, together with its ligand HGF, showed no significant expression differences to the mammal models, the ligand-receptor (HGF/MET) ratio difference between the human (HGF/MET = 0.56) and the mice (HGF/MET = 0.12) might result in the transduction failure of murine hepatocytes using the AAV3 vectors. Our results also showed ACE2 expression was not detected in the human liver, while low expression levels were observed in other species, suggesting that the liver might not be the main target of SARS-CoV2.

Conclusion

In summary, even though all model organisms have limitations, non-human primates or humanized animals are indispensable during drug development before proceeding to clinical trials.