Mouse Research

A Dirty Rat is a Healthy Rat

Boost Your Immune System

Gritty rats and mice living in sewers and farms seem to have healthier immune systems than their squeaky clean cousins that frolic in cushy antiseptic labs, two studies indicate. The lesson for humans: Clean living may make us sick.

The studies give more weight to a 17-year-old theory that the sanitized Western world may be partly to blame for soaring rates of human allergy and asthma cases and some autoimmune diseases, such as Type I diabetes and rheumatoid arthritis. The theory, called the hygiene hypothesis, figures that people's immune systems aren't being challenged by disease and dirt early in life, so the body's natural defenses overreact to small irritants such as pollen.

The new studies, one of which was published Friday in the peer reviewed Scandinavian Journal of Immunology, found significant differences in the immune systems between euthanized wild and lab rodents.

When the immune cells in the wild rats are stimulated by researchers, "they just don't do anything they sit there; if you give them same stimulus to the lab rats, they go crazy," said study co-author Dr. William Parker, a Duke University professor of experimental surgery. He compared lab rodents to more than 50 wild rats and mice captured and killed in cities and farms.

Also, the wild mice and rats had as much as four times higher levels of immunoglobulins, yet weren't sick, showing an immune system tuned to fight crucial germs, but not minor irritants, Parker said. He said what happened in the lab rats is what likely occurs in humans: their immune systems have got it so cushy they overreact to smallest of problems.

"Your immune system is like the person who lives in the perfect house and has all the food they want, you're going to start worrying about the little things like someone stepping on your flowers," Parker said.

Challenged immune systems - such as kids who grow up with two or more pets - don't tend to develop as many allergies, said Dr. Stanley Goldstein, director of Allergy & Asthma Care of Long Island.

Parker said his study has drawbacks because he can't be sure that the age of the wild and lab rodents are equivalent, although he estimates the ages based on weight. He also could not control what happened in the past to the wild rats to see if they had unusual diseases before being captured and killed.

It would have been more useful had Parker studied extremely young wild rodents because, according to the hygiene hypothesis, that's when the protection from dirty living starts, said Dr. Stuart Levy, director of the Center for Adaptation Genetics and Drug Resistance at Tufts University.

Human epidemiological studies have long given credence to the hygiene theory, showing that allergy and asthma rates were higher in the cleaner industrialized areas than in places such as Africa. Parker's studies, looking at animal differences, may eventually help scientists find when, where and how environmental exposure help protect against future allergies and immune disorders, said Goldstein, and Dr. Jeffrey Platt of the Mayo Clinic in Minn., both of whom were not part of Parker's studies.

Parker said he hopes to build a 50-foot artificial sewer for his next step, so that he could introduce the clean lab rats to an artificial dirty environment and see how and when the immunity was activated.

That may be the biggest thing to come out of the wild and lab rodent studies, Platt said: "Then all of a sudden it becomes possible to expose people to the few things (that exercise the immune system) and gives them the benefit of the dirty environment without having to expose them to the dirt."

Source: Associated Press 06.17.06

Social, Maternal and Aggressive Behaviors in Rodents

Many standard behavioral tests exist for the study of interactive behavior in mice and rats. In order to choose the most appropriate test for a research study it is important to understand something about the range of rodent social behaviors and what, specifically, behavioral tests are attempting to measure.

Rats and mice used in research are considered social species, meaning, in general, they prefer some form of group living. Species that live together must interact and so have evolved various behaviors that allow and facilitate group living. Environmental conditions and individual characteristics (e.g., sex, age, reproductive status, genetic background, etc...) are important in determining the form and amount of social interaction that occur within a group. In addition, sensory and motor abilities and health status can influence the expression of social behavior in individual animals. For example, an animal may be less willing to interact with others if it is ill or in pain. In another example, the sense of smell (olfaction) is extremely important in mouse communication and mice with olfactory deficiencies may behave quite differently than normal mice.

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THE EFFECTS OF AN ENRICHED ENVIRONMENT ON THE HISTOLOGY OF THE RAT CEREBRAL CORTEX

Marian C. Diamond David Krech Mark R. Rosenzweig

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The Diseases of Research Animals (DORA) website is a tool primarily designed to benefit veterinarians, veterinary students and residents involved in the care of animal species commonly used in research. Diseases and conditions affecting mice are listed by category and are arranged from most to least prevalent in the context of a research facility setting. This site includes relevant information, such as incidence, transmission, clinical signs, pathology and diagnosis. Figures illustrating clinical presentation and pathology are provided whenever possible to augment descriptions. The information on this site is not exhaustive, rather, it is meant to serve as a basic, solid and readily accessible reference, highlighting some of the most important aspects of the most common diseases of research mice.

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The Rats of NIMH

The ethologist John B. Calhoun coined the term "behavioral sink" to describe the collapse in behavior which resulted from overcrowding. Over a number of years, Calhoun conducted over-population experiments on Norway rats (in 1958-1962) and mice (in 1968-1972) While Calhoun was working at NIMH in 1954, he began numerous experiments with rats and mice. During his first tests, he placed around 32 to 56 rodents in a 10 x 14-foot case in a barn in Montgomery County. He separated the space into four rooms. Every room was specifically created to support a dozen matured brown Norwegian rats. Rats could maneuver between the rooms by using the ramps. Since Calhoun provided unlimited resources, such as water, food, and also protection from predators as well as from disease and weather, the rats were said to be in "rat utopia" or "mouse paradise", another psychologist explained.[8]

Following his earlier experiments with rats, in 1972 Calhoun would later create his "Mortality-Inhibiting Environment for Mice": a 101-inch square cage for mice with food and water replenished to support any increase in population,[9] which took his experimental approach to its limits. In his most famous experiment in the series, "Universe 25", population peaked at 2,200 mice and thereafter exhibited a variety of abnormal, often destructive behaviors. By the 600th day, the population was on its way to extinction.

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