Towards a more ethical animal model in biomedical research

Abstract

Since the early twentieth century, mice have emerged as the standard mammalian model organism for biomedical research. When pain relief is provided during experimentation, it typically comes in the form of transient and sometimes ineffective analgesics or anesthesia. This thesis proposes an alternative to the current method of research in the form of an engineered mouse model in which pain sensing can be ablated before an experiment. An ERT2-inducible Cre recombinase under the Wntl promoter was designed to be combined with a floxed Nav1.7 ion channel mouse model. When a 4- hydrotamoxifan class small molecule is fed to the mouse, Cre recombinase expression in the peripheral nervous system will disrupt function of the ion channel involved in inflammatory and mechanosensory pain. Additional designs for floxed Nav1.6 ion channel and Nax ion-like channel were made to explore disruption of peripheral cancer-induced neuropathic pain. In parallel with mouse model development, a survey was conducted to understand the potential for adoption of this new animal model by researchers. The survey was sent to IACUC members questioning if this model was needed, as well as how it may be regulated under the existing protocol approval framework. Results indicated that there is a both a need and desire for further refinement strategies within animal research, and that this inducible painfree mouse model could be categorized as alternative analgesic upon sufficient characterization and peer-reviewed publications. Additional input was provided that will shape testing done on the generated animals to assure that this model can mitigate animal suffering while still recapitulating important biological processes investigated in biomedical research.