SIGMOVIR Biosystems, Inc logo AAALAC_accred
Home Cotton Rat Model Research Sales and Contract Services Contact Us

       Cotton Rat Model           
  An unusual rodent live-trapped in the wilderness of
  the New World shows surprising permissiveness
  to some of the most dangerous human
  pathogens and becomes the “gold standard”
  model of RSV.

The cotton rat is considered the model of choice for Respiratory Syncytial Virus (RSV) studies because it recapitulates several characteristic features in the human disease. The cotton rat model accurately predicted the success of immunoglobulin prophylaxis (RespiGam®, MedImmune Inc.) against RSV bronchiolitis in the newborn population. Clinical trials of a second, more potent generation of immunoprophylactic therapy against RSV (Synagis®, MedImmune Inc.) were consented by FDA relying on preclinical data solely generated in the cotton rat . In theses clinical trials, Synagis® decreased the rate of hospitalization of high risk-infants up to 80%. In addition, the cotton rat closely recapitulated the devastating pathological outcome associated with the RSV-vaccine failure in the 1960’s. These achievements place the RSV cotton rat model as the “gold standard” for testing vaccines, antivirals and anti-inflammatory therapies against RSV.

The first use of the cotton rat in biomedical research occurred in 1937 and was related to poliovirus, rather than to RSV. At that time paralytic poliomyelitis had been produced in experimentally infected monkeys. However, scarcity and cost of these animals had severely limited their utility as a model for vaccine development. In an effort to identify a small-animal model, Dr. Charles Armstrong of the National Institute of Health dispatched his assistants to Florida and Georgia, with instructions to live-trap wild rodents. They returned with a wide variety of animals and injected them with a homogenate of spinal cord from an 18-year-old who had died of polio. Amongst all the species, only the cotton rat developed paralytic disease.

Over the ensuing decades the cotton rat has been shown to be a preferred model of an impressive list of human pathogens: RSV, influenza (A and B serotypes), adenoviruses (several serotypes), parainfluenza virus (type 3), measles, herpes simplex (types 1 and 2), human metapneumovirus, Staphylococcus species, Streptococcus species, and Mycobacterium tuberculosis. The permissiveness of a single, small laboratory animal for such a wide array of human pathogens is unprecedented. A few general observations may provide clues to the cotton rat’s unique utility:
  • Unlike the laboratory mouse, which either lacks or has defective Mx genes that are of great importance in the host response to infection, the cotton rat has fully functional Mx genes that appear to respond to infection in the same manner as human Mx genes.
  • The intracellular machinery of cotton rats differs markedly from that of laboratory mice, as evidenced by the fact that human immunodeficiency virus (HIV-1) productively infects cotton rat cells, yet is blocked by post-entry mechanisms in mouse cells.
  • RNA from RSV-infected cotton rat lungs reacts with double (about 600) the number of genes on a human gene chip as on a mouse chip (about 300).
Original Design and Technical support provided by Mosaic IT Solutions, Ltd (UK).