Rabbit as an Animal Model for Tuberculosis Research

The three main animal models employed for the study of tuberculosis (TB) pathogenesis in humans are rabbits, guinea pigs, and mice. All three of these species have the advantages of closely approximating clinical observations as they can be infected by inhalation, display both innate and adaptive immune responses, and generally control the infection initially before it finally becomes fatal. Human TB pathogenesis is a very complex process and no one animal model represents all aspects of the disease. However, rabbit models of TB have the further advantages of displaying cavitation and arrested infection. [1,2]

Rabbit is the only experimental model in which pulmonary cavitation occurs. Pulmonary cavities in rabbits and humans contain huge populations of TB bacteria (~108), which have access to the bronchial tree and therefore the external environment. Given that the degree of contagiousness of TB in humans is typically judged by bacillary burden in sputum culture, the study of cavitation in rabbits is critical to our understanding of TB transmission in humans. Further, the immune systems of rabbits are capable of arresting infection such that they display a latent, or paucibacillary, state similar to humans and in some cases are capable of controlling TB infection so effectively that the bacilli appear to have been completely cleared. While reactivation from a latent state is spontaneous in humans, rabbit reactivation requires immunosuppression. These features make rabbit an important model for the study of human latent TB. [1,2]

References
1. Bosze, Z. and Houdebine, L.M. (2006) Application of rabbits in biomedical research: a review. World Rabbit Sci. 14:1-14.
2. Dharmadhikari, A. and Nardell, E.A. (2008) What animal models teach humans about tuberculosis. Am. J. Respir. Cell Mol. Biol. 39:503-508.

Rabbit as an Animal Model of Human Disease

In the context of biomedical research, rabbits are perhaps most often thought of as bioreactors for the production of monoclonal and polyclonal antibodies and more recently recombinant proteins. However, rabbits are increasingly becoming a valuable experimental model in their own right and are in some cases, the translational model of choice. [1]

Rabbit models do not have the litany of advantages afforded by rodent, or for that matter invertebrate, models in terms of their short life spans, short gestation periods, high numbers of progeny, low inter-individual variability, low cost, advanced genomics and proteomics, and broad availability of reagents. However, rabbits do have many advantages and serve to bridge the gap between these small animal models, which are perhaps best suited for discovery phases of research, and larger animal models often required for pre-clinical, translational research. Rabbits are relatively inexpensive to purchase, house, and maintain as compared to larger animal models. They are easy to breed and handle and are a well-established model in terms of being recognized by the scientific and regulatory communities. Rabbits are phylogenetically closer to primates than rodents and further offer a more diverse genetic background than inbred and out-bred rodent strains, which makes the model a better overall approximate to humans. Further, rabbit genomics and proteomics are advancing rapidly and several transgenic lines have been created and characterized and are readily available. With more researchers using rabbits in their experiments, industry is catching up to their needs and offering an expanding range of rabbit-specific products and services to support them. [1]

Perhaps most importantly, there are some human conditions that cannot be adequately modeled by invertebrate or rodent species and in some cases, the special characteristics of rabbit anatomy and physiology make it uniquely suitable for the study of particular human diseases. [1] Some of the fields for which the rabbit often serves as a primary experimental model include atherosclerosis, Alzheimer’s disease, eye research, osteoarthritis, and tuberculosis. Below is a brief description of how rabbits are crucial to furthering research in these selected areas. This review is intended to be neither comprehensive nor definitive, rather an overview of selected biomedical research fields that employ the rabbit model.

References1. Bosze, Z. and Houdebine, L.M. (2006) Application of rabbits in biomedical research: a review. World Rabbit Sci. 14:1-14.