Guinea Pigs as an Animal Model of Human Disease

The guinea pig was first established as a valuable biomedical model in the field of bacterial disease in the 1800s and early 1900s, with works published on tuberculosis and diphtheria using guinea pig models each earning Nobel Prizes. While guinea pigs are a bit more expensive than mice and still lack the abundance of genomic and proteomic tools currently available for mice, they do offer several unique and important advantages. [1,2]

Biologically, guinea pigs have recently been re-classified as a non-rodent species and in many ways reproduce human disease more closely than rodents in terms of pathology and histology and therefore offer a more translatable model for the development and testing of new therapies. In particular, guinea pigs have greater similarities to humans (as compared to mice) in pulmonary physiology, innate and adaptive immune system physiology, the lack of ability to endogenously synthesize vitamin C, and many other aspects. Specifically, the guinea pig immune system has been heavily studied and found (again, as compared to mice) to have complement systems more similar to humans, infection-induced IFN-γ and iNOS expression patterns more similar to humans, and a number of important immune system genes including IL-12 p35 and p40, RANTES, CD8, and Leukocyte Antigen more similar to humans at the nucleotide or amino acid sequence levels. Further, unlike mice and rats, guinea pigs express a number of human-like CD1 homologs and express both IL-8 and its receptor CXCR1. [1,2]

Experimentally, guinea pigs are docile and easy to handle and are considered one of the smallest models with immunological relevance to humans. Further, they are less expensive to purchase, house, and breed than most of the other relevant animal models and experience short disease time courses, which facilitates rapid assessment of disease progression and testing of potential therapies. [1,2]

Currently, the Kingfisher Biotech portfolio of recombinant Guinea Pig proteins, includes CCL2 (MCP-1), CCL5 (RANTES), CCL11 (Eotaxin-1), CXCL1 (GRO alpha), IL-1 beta, and IL-8 (CXCL8).

References
1. Padilla-Carlin, D. et al. (2008) The guinea pig as a model of infectious diseases. Comp. Med. 58(4):324-340.

2. Hicky, A.J. (2011) Guinea pig model of infectious disease - viral infections. Curr. Drug Targets 12(7):1018-1023.

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.