Cotton Rats as Animal Model
Introduction
Cotton rats are an important animal model to study infectious diseases because of their unique susceptibility towards human pathogens. Whereas mice and rats are often not susceptible to human pathogens, replicate them at low levels or require rodent-adapted pathogen strains, the cotton rat has proven susceptible to a wide variety of human pathogens and to be a model system to simulate a number of important parameters of human disease. In addition to the study of infectious diseases, cotton rats have been used to study toxins in the environment and recently also as a tumor model.
In contrast to rats and mice, cotton rats are a new world rodent and live in the South of the USA, Central America and the North of South America. They often live in cotton fields. Apart from Sigmodon hispidus which is used in the laboratory a number of other Sigmodon species exists. Cotton rats have a brown coat, weigh 100 to 250 g, and have a body length of 12 to 20cm and a tail length of 8 to 15cm.
Cotton rats as models of infectious diseases
Cotton rats can be infected with a variety of human pathogens. In table 1 , pathogens are organized alphabetically within their respective group (viruses, bacteria, fungi and parasites).
Reagents and Methods
Chemokines and Cytokines
A large number of chemokine and cytokine genes have been cloned and ELISA and other antibody based systems are commercially available through R&D Systems. In addition, PCR assays have been established. For a summary see table 2 .
Antibodies
For a number of immunologically relevant cotton rat markers antibodies have been produced or cross-reactive antibodies have been defined which were produced for CD molecules of different species. In addition, a number of sera produced against intracellular molecules like AKT kinase, heat shock protein 72, COX 2 and others react well with the cotton rat counterpart. For a summary see table 3 .
Immunological methods
A variety of immunological methods have been established for the cotton rat so that immunological responses after infection or vaccination can be evaluated (table 4 ).
Inbred cotton rats
Cotton rats were inbred by the Veterinary Branch of the National Institutes of Health. Commercial suppliers for this inbred strain are (in the US) Harlan Inc., Ace Animals and Virion Systems, and in Europe Charles River. In addition, breeding colonies can be found at various universities worldwide.
Handling and housing
Cotton rats can be housed in type III (rat) cages with standard bedding and rodent chow on a 12 hour light/12 hours dark cycle. Cotton rats are not aggressive but bite when touched. Their tail degloves easily. The simplest way to handle cotton rats is the use of garden leather gloves or a handling device.
Anesthesia and euthanasia
For anesthesia isoflurane can be used with an anesthetic machine and for euthanasia CO2 inhalation.
Blood draw and application of substances
Blood draws have to be done under anesthesia and the best location is the retro-orbital venous plexus. Blood draws from the facial or tail veins have not been successful in our hands. Substances can be applied intranasally (depending on size up to 200μL), intraperitoneal, subcutaneously or intramuscularly.
References
Articles about the biology, use, handling and breeding of cotton rats:
- Niewiesk, S., F. Völp and V. ter Meulen (1997). A maintenance and handling device for cotton rat (Sigmodon hispidus). Lab Animal 26: 32-33.
- Niewiesk, S. and Prince, G. A. (2002). Diversifying animal models: the use of hispid cotton rats (Sigmodon hispidus in infectious diseases. Laboratory Animals 36: 357-372.
- Prince, G. A. (1994). The cotton rat in biomedical research. AWIC Newsletter 5: 3-5.
- Vaux-Peretz, F. and B. Meignier (1991). Le rat des cotonniers Sigmodon hispidus. Sci. Tech. Anim. Lab. 16: 5-17.
- Ward, L. E. (2001. Handling the cotton rat for research. Lab Animal Europe 1: 31-36.
A collection of references about cotton rats is available as FileMaker file (6MB: fp5 or fp7).
