Rabbit as an Animal Model of Alzheimer's Disease

As a result of the rarity of spontaneous Alzheimer’s disease (AD) development in non-human species, animal models mimicking various aspects of this disease have only recently been innovated – typically via dietary, pharmacological, or genetic manipulations. Of these new experimental AD models, the rabbit hypercholesterolemia model, originally developed for the study of atherosclerosis (described above), has a variety of advantages that make it one of the leading models for AD research as well. [1]

Physiologically at the cellular and molecular levels, rabbits fed high-cholesterol diets display many of the neuropathologies observed in humans with AD. The brains of these rabbits show increased levels of cholesterol and Amyloid β (Aβ) and decreased levels of acetylcholine, increased Aβ, tau, and ApoE immunoreactivity, Aβ plaques in the extracellular space, a breakdown in the blood-brain barrier, and an increase in microglial and decrease in neuronal cell populations. The phylogenetic proximity of rabbits and humans is reflected in the 97% amino acid sequence conservation observed between the two species’ Aβ proteins and is a major advantage over other models of AD including fruit flies, mice, and rats. Anatomically, rabbits have larger brains relative to the aforementioned species allowing for greater flexibility in testing for cognitive impairment. Cognitively, rabbits with hypercholesterolemia-induced AD display age-dependent deficits in associative learning that closely parallel those observed in humans. As measured by impairment of eyeblink classical conditioning, these deficits are beyond those observed with normal aging, are specific to AD (i.e., not observed in Parkinson’s Disease or Huntington’s disease), and are relieved upon administration of drugs that improve cognition. No other experimental animal model of AD boasts such an extensive body of existing data by which to judge cognitive impairment as the classically-conditioned eye blink response of rabbits. [1]

Reference1. Woodruff-Pak, D.S. (2008) Animal models of Alzheimer’s disease: therapeutic implications. J. Alzheimers Dis. 15(4):507-521.

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.