PBX mice are specialized laboratory models engineered to contain human liver cells, serving as a bridge between preclinical animal studies and human clinical trials. These “humanized” mice address the limitations of traditional animal models, which often fail to accurately predict human drug responses due to species-level differences in metabolism and physiology. By providing a living system with functional human liver tissue, PBX mice enhance the relevance of research findings, accelerating the development of new drugs and therapies.
Understanding PBX Mice
The term “PBX” in PBX mice specifically refers to PhoenixBio’s proprietary PXB-mouse®, a chimeric mouse model with a highly humanized liver. These mice are created by transplanting primary human hepatocytes into immunodeficient mice, typically uPA/SCID mice, whose own liver cells are damaged by the expression of urokinase plasminogen activator (uPA). The transplanted human hepatocytes engraft and repopulate the mouse liver, often achieving over 70% human hepatocyte engraftment, sometimes reaching 95%.
This genetic modification allows the PXB-mouse liver to exhibit normal human liver histology and function, including the secretion of human albumin and human-type bile profiles. The humanized liver also expresses human xenobiotic metabolizing enzymes and transporters, important for drug metabolism studies.
Applications in Scientific Research
PBX mouse models are widely utilized to overcome translational challenges in drug discovery, offering more accurate prediction of drug pharmacokinetics, efficacy, and hepatotoxicity in humans. Their humanized livers process compounds similarly to human livers, making them useful for assessing drug metabolism, safety, and hepatotoxicity of new drug candidates.
These models are also used in infectious disease research, especially for human-specific infections like hepatitis B (HBV) and hepatitis C (HCV), as they support durable viral replication at levels observed in humans. Beyond drug development and infectious diseases, PBX mice are used in emerging fields such as gene-editing research, providing a human liver environment for testing gene therapies. Researchers can also isolate human hepatocytes, known as PXB-cells, from these mice for in vitro studies, allowing for a direct comparison between in vitro and in vivo data using the same human cells.
Key Discoveries from PBX Mouse Models
Studies using PBX mouse models have provided significant insights into human liver function and disease. Researchers have characterized gene expression levels in PXB-mouse livers, finding them similar to those in normal human livers. This similarity extends to the metabolic zonation of enzymes like glutamine synthetase and cytochrome P450 2E1, mirroring patterns in human livers.
The models have been important in confirming the ability of human liver cells to support persistent viral infections, such as HBV and HCV, offering an authentic in vivo setting for studying viral pathogenesis and evaluating antiviral therapies. Furthermore, the development of human albumin ELISA kits for PBX mouse serum has enabled researchers to differentiate human hepatocyte-specific damage in toxicological studies, providing a more precise understanding of drug effects on human liver cells. These advancements highlight the contributions of PBX mouse models to understanding human biology and improving drug development.