Eek, A Genetically Modified Mouse!
Consider the humble mouse. The trigger of many a phobia, mice have startled the daylights out of most of the world’s population, damaged uncountable homes, and turned tons of personal possessions into shreds. Mice like to party through the wee hours of the morning, squeaking and screaking like tiny gothic hinges, while we grumble and check the alarm clock every 20 minutes.
Particularly discouraging, mice eat 15 to- 20 times a day, yet remain tiny little things.
And, of course, mice can carry more than 100 human pathogens. Mice, it would seem, are naughty by nature.
Still, the mouse is easy to admire. It can jump like Michael Jordan, climb like Tensing Norgay, and swim like Katie Ledecky. And, for more than a century, mice have been helping to save the human race.
When scientists began working with mice, they didn’t know anything about DNA, and had only slightly more knowledge about genes. Around 1900, the scientific community rediscovered Mendel’s laws and wondered if his work — based entirely on plants — might explain all aspects of inheritance from individuals in other species groups, including in ourselves or other mammals.
The mammal these scientists were most interested in learning about was the human; it was also the animal they could not use for genetic studies.
Mice were the obvious choice for research. Small, gentle and easily housed, they adapt well to new surroundings and reproduce prolifically. A female house mouse can give birth to a dozen or more offspring every four weeks, or about 150 per year. Mice have a naturally short lifespan, so several generations can be observed in a relatively short period.
Collections of mice were readily available in Victorian England. Mouse fanciers were already breeding the little creatures to produce coats of more interesting colors and patterns.
Many of today’s most popular laboratory mouse strains are direct descendants of those original “fancy mice.”
The period of 1900-1911 yielded important developments in the subjects of inheritance, mutation, and the differentiation of genetic traits. However, two world wars, a global recession, and an influenza pandemic slowed scientific advancement in genetics to a crawl for 30 years.
In the early ‘70s, scientists produced the first recombinant DNA molecules and cloned the first animal gene. In 1974, researchers created the first mice with foreign DNA inserted into their genetic material. The inserted genes were present in every cell, but the mice did not pass the transgene to their offspring.
In 1981, the first transgenic animal was created in which the transferred gene would be expressed in the mouse and its future offspring. The ‘80s and ‘90s exploded with advancements in genetics.
Mice were the research vehicle of choice a century ago for reasons that were logical, but largely convenient. The decisive factor in their furry little favor as research animals came later: the genetic, biologic and behavior characteristics of mice closely resemble those of humans. Mice naturally develop conditions that mimic human diseases, such as cancer, Alzheimer’s disease and diabetes.
Developments during the past 20 years have allowed researchers to create custom-made mice through gene targeting in mouse embryonic stem cells. Site-directed mutagenesis is the molecular biology method used to make these specific, intentional changes to the DNA sequence of a gene. The most frequent use of the technique is to make “knockout” mice — animals genetically engineered so they lack a specific gene, which allows researchers to study gene function as it relates to the entire organism.
By observing what happens to animals with certain genes removed, researchers can identify the function of the gene, and whether it is linked with a disease or faulty embryonic development. Armed with this knowledge, they can then produce and test new drugs to combat that disease.
These genetically modified mice have offered huge amounts of information about the function of an array of mouse genes and their human counterparts. As breakthroughs in science go, few in recent decades have been larger than the creation of genetically modified animals.
Selectively bred mice play a critical role in developing the medical wonders of today and tomorrow. Yet, developing unique, genetically modified strains of mice for their own studies would be a costly and time-consuming process for most biomedical researchers. So, where does the global research community find all these mice?
Research scientists in fields from immunology to cancer can save time and money by acquiring genetic material from a repository of previously engineered strains, such as the University of Missouri’s Mutant Mouse Resource and Research Center.
The MU-MMRRC imports, stores and distributes a vast number of mutant mouse and rat strains and embryonic stem cells for research. It is one of only four such centers in the United States. The purposes and pertinence of research rodents articulates the importance of the MU-MMRRC, whose primary function is to supply biomedical investigators with the necessary components for their research.
Currently, the MU-MMRRC houses 3,882 mouse strains and counting. In 2016, they distributed 208 mice from 28 different strains to researchers at 36 institutions across the United States and to 33 institutions in 16 other countries.
MU hasn’t stopped with mice. Researchers also work with a close relative — the rat, and an even larger animal — the pig. Rats are not just big mice; they have been invaluable to areas of biomedical research where the mouse has not replicated human disease such as behavior, cardiovascular disease and transplantation. To this end, MU is also home to the Rat Resource and Research Center (RRRC), the only resource of its kind that produces and distributes valuable rat models. The National Swine Resource and Research Center (NSRRC) is also located at MU developing pig models to study and develop treatments for human disease and organ transplantation research. Swine are even closer relatives to people and are required when researchers need a model that is similar in size to people.
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