The Rat Pack
Research Models
|
Regina Kelder

The Rat Pack

Charles River recently aided in a study involving wild rats who, let’s face it, represent a much different “clientele” than the well-bred laboratory rats we traditionally work with on a daily basis.

Charles River’s diagnostic lab—known the world over for its animal testing services—provided advice and technical support to a research group that has been diligently studying rats living on the city streets of Vancouver. The aptly named Vancouver Rat Project is concerned with understanding urban rat ecology, natural rat disease, and identifying known and—perhaps more importantly—unknown pathogens that urban rats are carrying, known as zoonoses, which could potentially be passed on to humans.

Dr. Charles Clifford, Director of Pathology and Technical Services at Charles River in Wilmington, said his division got involved when the Canadian scientists found pneumonia while doing histopathology of diseased tissues from several hundred rats. The rats had been trapped and collected from the city’s struggling Downtown Eastside neighborhood. The team was naturally curious about the cause of the pneumonia, and they wanted to collect more data, so one of their veterinary pathologists turned to Clifford for advice on how to proceed.

Detective Work
Clifford suggested they conduct a general survey of the population using collected serum samples first to see which of many possible infectious diseases were present in the larger group, before embarking on a more focused molecular investigation aimed at nailing down the source or sources of the pneumonia in affected individuals. “That way we could find out what the rats had generally been exposed to,” said Clifford.  Any positive results from the general survey could then be followed up with more fine-tuned [molecular testing] on the actual tissue samples where the disease was observed, he added.

Clifford said of the hundreds of rats initially trapped and tested, standard blood screens were ordered for 10 of the largest (and presumably oldest) rats that came from different city blocks. Scientists checked for a full panel of 18 agents that might potentially infect rats.  (It should be noted that many of these respiratory diseases probably once infected the average lab rat, but the microbes have largely been removed from these protected populations through rederivation, careful breeding, the use of pathogen-free animal facilities, and quality care.)

Frozen lung tissue from rats are currently being analyzed using polymerase chain reaction (PCR) technology—a service Charles River excels at performing—to try and detect the genetic footprints of certain bacteria and fungi.

Veterinarian Jamie Rothenburger, a resident specializing in anatomic pathology at the University of Saskatchewan’s Western College of Veterinary Medicine and one of the Canadian co-investigators in the Vancouver rat project (along with colleague Ted Leighton who is also with the Canadian Cooperative Wildlife Center and Chelsea Himsworth with the University of British Columbia) said she suspects the rats may have been infected with either Pneumocystis  carinii  (a primary pathogen in immune-compromised rats), Mycoplasma pulmonis  or cilia associated respiratory bacillus. But she said lab won’t know for sure until later in November, when the tissue analysis will be finished.

Rat Profiling
Vancouver scientists embarked on their project—which they described as the only comprehensive study of the health and zoonotic pathogens of rats—so that they could fill in gaps about a rodent population that most people would agree is a public nuisance but which epidemiologists don’t typically track all that well. Rats may shoulder the blame for sparking the Black Plague in Europe during the Middle Ages—the bacteria that causes plague is believed to have been spread by fleas living on the backs of black rats—but researchers know surprisingly little today about the pathogens that common rats harbor and could pass on to humans.

During the initial phase—and before Charles River became involved—Canadian scientists screened more than 700 rats for diseases ranging from Seoul Hantavirus—the source of Korean hemorrhagic fever—and the parasite-driven toxoplasmosis. Scientists uncovered cases of leptospirosis, a bacterial disease that in severe cases can lead to kidney failure. Leptospira—an extremely fragile bacteria—is more typically found in the developing world, though there have been examples of rat-borne leptospirosis in France and Baltimore. The Canadian team published results of their findings from that initial survey in a PLoS One journal in June.

“The biggest question with urban rats is we don’t know why they die.” said Rothenburger. “Some interesting studies show their life span in the wild is less than a year of age, but in a laboratory they can live up to three years.”

Rothenburger said diseases could be an explanation for the rapid turnover, but because the study found a lot of significant disease in many different organ systems of the wild rats, they decided to focus just on respiratory diseases in the nose, trachea and lungs.

Given the fact that 40% of all mammals are rodents, why is there a lack of knowledge about wild rats? “From a natural disease perspective, it’s a matter of the “ugh” factor, people are disgusted by them and I guess some feel like they don’t merit scientific evaluation in their own right.  Also, no one has thought about the interaction between their natural diseases and those pathogens rats can transmit to people” said Rothenburger.

Readers can find more information about this research project at www.vancouverratproject.com.


References:

  1. PLoS One Negl Trop Dis 7(6): e2270. doi:10.1371/journal.pntd.0002270.