ToxReporter Mice
CXR Biosciences has developed the ToxReporter Mice concept for the rapid, mechanistic assessment of potential toxic effects in vivo.
A transcriptionally regulated 'stress' promoter from a gene involved in a pathway of toxicity is used to drive the expression of two reporter proteins:
Any compound that causes induction of the stress promoter induces expression of the reporters. The excreted hCG biomarker reporter enables real-time and non-invasive tracking of the stress response via blood and urine analysis. The LacZ reporter, via immunohistochemistry, enables identification of the precise target organ and cellular location of the stress response.
These animal models are undergoing evaluation and complement the in vitro Toxicity Reporter cell lines which CXR, and partner Millipore, have developed and validated.
To date CXR has developed transgenes to several different stress promoters that are associated with biochemical pathways involved in around 80% of the toxic responses to drugs, including ToxReporter Mice for:
Benefits
This approach provides a means of studying the relationship between chemical exposure and toxic response in a time- and dose- dependent manner in a single mouse
Effects will be observed prior to the onset of overt toxicity
Location specific, mechanistic tox readout
Download the ToxReporter Mice presentation here.
Humanised and knockout ADMET mice.
Key murine genes involved in the metabolic response to drugs (e.g. PXR, CAR, cytochrome P450s, drug transporters) are replaced with their human equivalents to give a more predictive and “human-like” response.
