Generating tissue-specific Cas9 rat models for the research community

Animal models are central to biomedical research for understanding disease pathology and testing scientific hypotheses in a controlled, reproducible setting. Both rats and mice are widely used for their genetic resources and their close relationship to humans. Preclinical studies in animal models are essential for understanding disease mechanisms and for drug testing. There are strong reasons to use either rats or mice in studies, and rats are overwhelmingly preferred in research across cardiovascular, neuroscience, physiology, and behavioral sciences. While rats are extensively used, testing a gene target for its role in biology, health, disease pathology, drug screening, and intervention response has been limited by a lack of effective genetic manipulation methods, antibodies, knockouts, and associated costs. While rats and mice are widely used, they are not mutually interchangeable with respect to functional mechanisms, alternative pathways, drug responses, phenotypes, pathology, or behavior, as these can differ dramatically. The availability of a mouse model, and the costs alone, should not compel a study to compromise by using a mouse model or cell culture models. To protect the integrity of the study and maintain the advantages of rat models, we will address a gap: the lack of readily usable rat models. We will develop three high-quality tissue-specific (heart, kidney, and brain) CRISPR (Cas9) rat models, assess their quality, and evaluate their utility for generating tissue-specific (heart) knockouts using three different methods.