Since human hepatocytes retain and exhibit normal function in the PXB-Mouse liver, the toxicities of the test articles to the human hepatocytes can be observed directly.
The PXB-Mouse has a big advantage to other animal models – the histological observation of the PXB-Mouse liver allows us to directly observe the toxicities to the human hepatocytes, as well as a simultaneous comparison of rodent hepatocytes.
The liver toxicities are detected by serum biomarkers such as the enzyme activities of ALT and AST. Additionally, since PhoenixBio recently developed our proprietary method to measure human ALT1 protein, the human specific liver toxicity can be detected from the PXB-Mouse serum unaffected by the deviation enzymes from the host animal hepatocytes.
Over 95% of mRNAs which express in the normal human liver also express in the PXB-Mouse liver. The change of the expression of human specific mRNA and/or micro RNA by the administration of test articles can be observed.
Human liver toxicity can be predicted via the exhaustive search of microarray analysis of the expression level of each gene in the PXB-Mouse liver, as well as by pathway analysis such as Apoptosis, Inframation (NF-kB signaling), etc.