CCL2 Homology Across 8 Species

Chemokine (C-C motif) ligand 2 (CCL2), also known as monocyte chemotactic protein-1 (MCP-1), is a small cytokine belonging to the CC chemokine family. There are at least 27 distinct members of the C-C subgroup reported for mammals. They are characterized by two adjacent cysteines. CCL2 (MCP-1) recruits monocytes, memory T cells, and dendritic cells to sites of tissue injury and infection. CCL2 (MCP-1) is implicated in pathogeneses of several diseases characterized by monocytic infiltrates, such as psoriasis, rheumatoid arthritis and atherosclerosis.

MCP-1/CCL2 Homology Across Species

Kingfisher Biotech has Bovine CCL2, Canine CCL2, Equine CCL2, Guinea Pig CCL2, Rabbit CCL2, and Swine CCL2 products, including proteins, antibodies and ELISA VetSets.

Rabbit as an Animal Model for Atherosclerosis

Atherosclerosis naturally occurs only in humans, a few non-human primates, and pigs. Rabbits, being herbivores, do not develop atherosclerosis naturally, but do consistently develop an atherosclerotic condition that very closely resembles clinical observations when manipulated via dietary or genetic interventions. The rabbit hypercholesterolemia model is perhaps the most well-know of the models and is typically produced by feeding intact rabbits a high-cholesterol diet. After only a few weeks on a modified diet, rabbits develop notable vascular lesions. This rabbit model is highly reproducible with minimal variation between animals in a single laboratory and between laboratories. Two spontaneous lipid metabolism mutants have been characterized and also used extensively in atherosclerosis research – the Watanabe heritable hyperlipidemic (WHHL) rabbit (LDL receptor deficient) and the St. Thomas’ Hospital rabbit (VLDL, IDL, and LDL elevated) serve as models for familial hypercholesterolemia and familial combined hyperlipidemia, respectively. Homozygous WHHL rabbits and St. Thomas’ Hospital rabbits predictably develop atherosclerotic lesions on normal diets. Finally, there are at least 19 transgenic rabbit lines now available specifically for the study of cardiovascular disease that express a wide variety of human transgenes many of which code for proteins implicated in atherosclerosis. [1-3]

These rabbit models closely approximate a variety of aspects of human atherosclerosis and are commonly used to study atherogenesis, plaque instability and rupture, and myocardial infarction. Relative to rodent models, rabbits are much more clinically relevant as many aspects of rabbit lipoprotein metabolism are very similar to humans. Perhaps the most notable differences are that rabbit vascular lesions are more fatty and more inflammatory (as measured by numbers of macrophages present) and rabbit circulating cholesterol levels are higher. An additional advantage to rabbits over rodents is that human transgenes expressed in rabbits produce the expected human-like symptoms while the same transgenes expressed in rodents fail to do so. Further, rabbits are capable of tolerating longer experimental protocols that require monitoring and/or sampling over a period of time whereas individual rodents often can only contribute to a single time point in a study. [1-3]

Rabbit is the first and classical model for human atherosclerosis research and will continue contribute pre-clinical, translational evidence for the safety and efficacy of novel therapies. Perhaps the only animal models that have in some cases surpassed the value delivered by rabbits are the swine models. [1-3]

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

2. Badimon, L. et al. (2008) Models of behavior: cardiovascular. In: Conn, P.M. (ed.) Sourcebook of models for biomedical research. Humana Press, pp. 361-368.

3. Kónya, A. et al. (2008) Animal models for atherosclerosis, restenosis, and endovascular aneurysm repair. In: Conn, P.M. (ed.) Sourcebook of models for biomedical research. Humana Press, pp. 369-384.

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.