100 years of the laboratory mouse

Maxim Russo, Be Healthy magazineIn 2009, the world celebrates the centenary of the laboratory mouse.

But why exactly a century, if experiments on mice were carried out in the XIX century, first by physiologists, and then by microbiologists? For example, in the 1870s, Robert Koch proved on mice that the bacterium he discovered causes anthrax. In the early years of the XX century, Paul Ehrlich performed more than a thousand experiments trying to transfer a tumor from one mouse to another.

The first clean line

What happened in 1909? To deal with this, we must remember that completely identical objects are needed for scientific experiments: the first one is where the experiment is put, and the second one is a control one. When experimenting on living organisms, they must be genetically identical plants or animals, for which it is necessary to resort to inbreeding – closely related crossing. Offspring are obtained from siblings, among this offspring, brothers and sisters are mated again. This has been done for several generations. As a result, animals are obtained whose genotypes completely coincide. Such offspring are called inbred line (sometimes the term "pure line" is also used). Inbred animal lines are also good because such animals can be transplanted tissues and organs from each other without causing rejection.

The first inbred mouse line suitable for research was obtained in 1909. It was developed by Clarence Cook Little (1888 – 1971) from Harvard University. He was studying how the coloration of mice is inherited. In the course of his work, he decided to get genetically identical mice by inbreeding and was successful. This was the first pure mouse line known as the DBA line and still exists today. Mice of this line have a light brown color.

In order to get genetically homogeneous mice, it is required to cross siblings for 18-20 generations. This is where one of the most advantageous features of a mouse as a laboratory animal manifests itself: rapid reproduction. Mice reach sexual maturity at the age of 5-7 weeks, their pregnancy lasts only 20 days. So, in a relatively short time, you can get several generations. Clarence Little's work on bringing out the first clean line took only a few years.

The speed of reproduction is not the only advantage of a mouse as a test animal. Mice are unpretentious, they are easy to feed, they are small in size. The mouse serves as a good model of biological processes occurring in humans. "The mouse is the key to understanding the genetic basis of the development of the human body, its diseases and disorders of its functions," said Clarence Little. Of course, a pig or a monkey is even closer to a person, but it is much more difficult to keep them. Therefore, from 1909 to the present day, millions of mice live in laboratories around the world.

In fact, Little was not the first creator of a pure line of mice. This, though not at all for research purposes, was done back in the XIX century by mouse lovers in Japan. They fixed a mutation in the offspring of mice by closely related crossing – a violation of the pituitary gland and vestibular apparatus. As a result, these mice often start spinning quickly in one place. This breed is called "dancing mice".

Laboratory mice on an industrial scaleIn 1929, Clarence Little founded the Jackson Laboratory in Bar Harbor, Maine, which became a center for research on genetics and at the same time a base for the production of pure mouse lines.

It was named in honor of Roscoe Jackson, the head of the Hudson Motor Car company, who financed the creation of the laboratory. By 1944, the Jackson Laboratory was supplying 9,000 mice weekly to other U.S. laboratories. Research work was also carried out in it. In 1947, during a fire, the laboratory was destroyed, but it was quickly restored, and the number of mice was replenished thanks to animals sent by scientists from all over the world who had previously received mice from the Jackson laboratory.

Now the Jackson Laboratory is a world–famous scientific center where research is conducted in many areas, for example, on mammalian genetics and oncological diseases. At the same time, this laboratory serves as a major training center for specialists in molecular biology. And, of course, the Jackson Laboratory is still the leader in the cultivation of laboratory mice: now it annually supplies about two million animals to scientific institutions around the world.

Many important discoveries were subsequently made in the Jackson Laboratory. For example, George Snell, who worked there, with the help of experiments on mice, discovered genetic factors that determine tissue compatibility during organ transplantation. He discovered a region of the genome called the "major histocompatibility complex". The genes of this region encode certain proteins located on the surface of cells and play an important role in the work of the immune system. In 1980, George Snell received the Nobel Prize for his work.

Experiments on mice

Bacteriologists, starting with Koch, infect mice with various diseases, pharmacologists test new drugs on mice. Mice serve as an indispensable object for experiments in the field of oncology, immunology, transplantology and other fields of medicine. Psychologists and psychophysiologists study the mechanisms of memory and orientation in mice, forcing animals to go through special mazes. When genetic engineering technologies appeared at the disposal of scientists, mice were again needed. Whatever genes were introduced into mouse chromosomes – including genes associated with obesity, increased aggressiveness or alcoholism.

A lot of discoveries have been made with the help of mice. Here is just one of the recent ones. In 2007, Mario Capecci, Martin Evans and Oliver Smithies received the Nobel Prize in Physiology or Medicine "for their discovery of the principles of making specific gene modifications of mice using embryonic stem cells." That is, it was Martin Evans in 1981 who first isolated lines of embryonic stem cells from a mouse embryo.

As a result of the research of Capecci, Evans and Smithies, so-called "knockout mice" appeared in the laboratories. They are blocked ("knocked out") individual genes, which allows us to study the functions of these genes or simulate human diseases in mice.

Rusty, a laboratory mouseNowadays there is a whole industry for growing laboratory mice.

For the needs of scientists, various pure lines of mice with the necessary properties have been created. The famous BALB/c (Bagg albino C) line of large white mice was created by Halsey Bugg from New York by crossing mice he received from a supplier from Ohio. Bugg has been crossing siblings for 26 generations and eventually got one of the most popular lines in the world's laboratories. In 1951, the National Institute of Health of the USA began to preserve the line, at that time its history numbered 72 generations. BALB/c mice are used in immunology and oncology research.

Mice of line A and many of its sublines are characterized by an increased incidence of breast cancer. AKR/J mice often suffer from leukemia, BRSUNT/N mice are prone to obesity, CBA/CaLac mice are distinguished by longevity. The I/StY line is highly sensitive to the causative agent of tuberculosis, and the 101/H line is highly sensitive to the induction of skin and lung tumors. There is also a hairless line – HRS/J. When growing any line, the genetic identity of the offspring is controlled after a certain time, and mice in whose body mutations have occurred are culled. For work that does not require absolutely identical animals, mice that do not belong to clean lines are also raised. They go on sale under the name "nonlinear mice".

For the work of immunologists, mice with suppressed immunity are required. They are also used in oncology research. Strains of various tumors are stored in laboratories, and a scientist no longer has to wait for a tumor to spontaneously develop in a mouse, he can transplant a strain of the desired tumor to it. This allows for much faster research on the treatment of oncological diseases. A line of mice with immunodeficiency has been created for such work. These mice lack a thymus (thymus gland) and a hairline. They are known as "naked mice" (nude mouse). To work with them, special sterile vivariums are created, sterile sawdust and food are used, since these mice can easily become a victim of any infection.

In addition to the mice themselves, manufacturers offer "related products". First of all, this is a special feed. In addition, there is a variety of equipment: from simple wheels and mazes, to specially designed X-ray machines and tomographs for mice. You can do an ultrasound and a cardiogram of the mouse.

A mouse cast in bronzeMonuments have been erected to many animals that helped scientists in their work.

Laboratory mice are also not ignored. In Russia, such a monument is installed near the veterinary laboratory of the city of Zadonsk, Lipetsk region.

And the monument to the laboratory mouse, which has been planned to be erected near the Novosibirsk Medical Academy for several years, for some reason is not lucky. In 2005, the monument project was commissioned by sculptor Aram Grigoryan: out of seven models made by him, Novosibirsk doctors chose one, but then she went to Moscow for revision. A laboratory mouse, hiding in a two-meter human palm, is sculpted in clay and still can't wait to be cast in bronze: the leadership of the Novosibirsk Medical Academy explains that there are not enough funds to finish work on the monument.

Portal "Eternal youth" www.vechnayamolodost.ru17.03.2009