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This project aims to revolutionize the study of urinary incontinence by introducing zebrafish as a novel genetic model for urinary sphincteric dysfunction. Unlike the current paradigms, which emphasize neurologic or traumatic/anatomic causes, this work will set the stage for a genetic animal model of incontinence using the unparalleled transparency, genetic tools, and scalability of zebrafish. The ability to directly visualize and manipulate sphincteric function in zebrafish will offer new insights into the genetic regulation of continence development and provide a framework for targeted therapeutic interventions. This model will challenge existing paradigms and offers a transformative approach to understanding sphincter function with targeted interventions. The project will establish a phenotyping platform to assess urinary incontinence using pH-sensitive indicators, dramatically increasing the rate and scale of future screening studies. This approach will enable rapid functional interrogation of genetic contributors to incontinence. This work will be coupled with foundational work mapping the transcriptomic and protein landscape of urinary sphincter development in zebrafish. By identifying genetic, neuronal, and muscular maturation processes at key developmental stages, this study will provide the first comprehensive understanding of functional continence development. If successful, this project will reshape the field by shifting incontinence research from purely surgical and neurological perspectives to a genetic and developmental framework. This could pave the way for precision medicine approaches, such as genetic risk prediction, targeted gene therapy, and non-invasive interventions for urinary incontinence. By leveraging zebrafish as a scalable and genetically tractable model, this study has the potential to disrupt the field and provide groundbreaking solutions for millions affected by incontinence.
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