Research | NCRM

Rabbits offer great potential as translationally relevant models of human disease for many biomedical research applications thanks to their evolutionarily closeness to humans, favorable reproduction features, relatively long lifespan which allows for clinically relevant studies, a body size that is similar to that of human infants allowing for more relevant surgical models, and an economically feasible housing cost in a research setting. Rabbit models have been critical to diverse scientific breakthroughs, including the development of invitro fertilization techniques, the HPV vaccine, and a multitude of antibodies for various scientific applications. Over the last 30 years, rabbits have been surpassed by mice in part due to ease of generating genetically engineered mice from embryonic stem cells (ESCs), which is not available in rabbits. CRISPR/Cas9 coupled with a complete rabbit reference genome has made it possible to generate gene edited (GE) rabbits analogous to those in mice for use in research. Other GE large animal models including pigs and non-human primates have also been generated, but the extended generation times, cost of housing, and high level of technical care required greatly limit how widely they can be utilized. GE rabbits overcome many of these barriers and allow for the development and expansion GE rabbit colonies in limited space and in a short time frame, making them a large animal that is practical for wider adoption. More than 50 GE rabbit models have been published thus far highlighting their usefulness, yet the cost of generating these models can be significantly higher than mice and rats. 

Here at NCRM we have developed a genome editing pipeline coupled with an improved rabbit reference genome for efficient generation of GE rabbits. We have also developed significant technical expertise in rabbit embryology and cryopreservation uniquely positioning us to expand the generation and maintenance of GE rabbits. We have generated different translationally relevant GE rabbit lines, including whole body knock-outs, humanization of disease associated alleles, and targeted knock-ins of proteins of interest. We have also established expansive expertise in characterizing these GE rabbits to study human disease and have demonstrated that for multiple diseases rabbits are superior to rodents due to increased translational relevance. However, rabbit models have increased costs and require advanced technical skills to generate which has limited the overall number of genetically edited rabbits generated and distribution of existing models. As a national resource center, the NCRM mission is to expand the access to gene edited rabbit models across the United States for their use in biomedical research. We are dedicated to generating novel gene edited rabbit models with direct translational relevance to human diseases, to disseminating these models to researchers across the nation, and to providing training workshop to potential users on these novel models and related technologies.