Animal model and resource development for preclinical lower urinary tract research

PROJECT SUMMARY Neuromodulation is routinely used to treat overactive bladder, and more specifically urgency urinary incontinence. Despite the therapeutic benefits of neuromodulation there remains room for improvement. Preclinical animal models may be useful for elucidating the mechanisms of action of neuromodulation to improve efficacy as well as to motivate new forms of neuromodulation. Recent work in our lab has suggested that chronic electrical stimulation in animals, mimicking what is done in humans, may be critical for understanding the mechanisms of neuromodulation. Although mouse models can be advantageous due to the wide variety of genetic tools available for working with mice, executing chronic peripheral nerve stimulation would be exceptionally challenging in mice. Rats are commonly used for studying the effects of acute neuromodulation, but the animal models of overactive bladder and urgency incontinence are lacking. Instead, healthy animals, or animals given chemicals to irritate their bladders (which may be more indicative of a pain model) are used, with the hope that results translate. To test chronic neuromodulation in rats, as well as to test other OAB therapies, there is a need for better rat models of OAB. As part of this Catalytic Tool and Technology Development grant we propose the creation of dataset that measures urological function in 8 different rat strains at various points in time in their lifespan. Strains have been chosen due to their characteristics which we think may impact their urological function (e.g., hypertension, obesity, diabetes, etc.). We expect the data from the various rat strains to provide insights into how the urological function differs in these strains, providing guidance to investigators who wish to use these strains in their urological research. This dataset, along with other previously collected datasets, will be made public in a data portal designed specifically to facilitate the sharing and reanalysis of preclinical urological data. Additionally data analysis tools will be created and made public to facilitate consistent data analysis across studies.