10 Human Diseases We Give to Mice
Scientists can obtain all kinds of useful information about human health, thanks to mice, one of the most widely used research (experimental) animals today. Practices such as injecting, infecting, and dissecting mice make it possible to access this information. However, many diseases only affect humans. Scientists need to be creative to study these diseases on mice. Using creative techniques such as hormone therapy, tissue transplants, or gene transfer, scientists “humanize” mice a little more, and it is possible to study many diseases specific to humans.
Sometimes, as with complex psychological disorders, modeling the disease in mice is more difficult (unpredictably) than it seems. Therefore, scientists may have to simply mimic a few symptoms rather than mimic the entire disease.
Gonorrhea is sexually transmitted and caused by a bacterium called Neisseria gonorrhoeae, transmitted only to humans in nature. Therefore, scientists who wanted to model this disease in mice in a laboratory environment first tried injecting N. gonorrhea into the vaginas of mice with the help of a syringe. However, no infection occurred because these bacteria did not like to live in mice.
In the search for a solution to this problem, a very short period was discovered in the mouse vagina during the oestrus cycle in which the conditions necessary for N. gonorrhoeae to develop and cause disease was discovered. Because this time frame is normally very short, the scientists were able to extend this time frame by administering the female sex hormone 17β-estradiol to mice. The administration of this hormone allowed the mouse vagina to accommodate N. gonorrhea for days, as it caused an increase in estrogen.
With these mice, scientists were able to test new drugs. However, they also got the chance to examine why an infection does not usually confer long-term immunity. As with humans, mice can become infected again after surviving the initial infection.
People with gonorrhea often have a concurrent chlamydia infection. To study this dual infection occurrence, scientists produced double STD (sexually transmitted diseases) mice. To create these models, two types of bacteria are injected into the vaginas of mice: C. muridarum followed by N. gonorrhoeae.
2) Alzheimer’s Disease
Alzheimer’s Disease is a degenerative disease that affects the brain and can cause severe memory loss. In the brains of the patients, many protein clusters called plaques made up of parts of the protein called APP, begin to form.
There are many ways to breed mice that have this disease. For example, it has been observed that the mice produced using the mutant APP form develop Alzheimer’s Disease. This mutant form of APP was first identified in two Swedish families. In these families, unusually early onset of Alzheimer’s has been noted due to the mutant APP while the patients were still in their fifties.
Memory loss occurs in many mice modeled for Alzheimer’s Disease. There are two tests used to measure the extent of this memory loss: the Morris water maze (Morris Water Maze) and the novel object recognition test (Novel Object Recognition Test).
In the first test, the mice are dropped into a pool. There is a hidden platform under the water placed inside this pool. Since mice do not like water, they look for a place where they will have less contact with water. After finding this platform, the mice are taken out of the water. After a certain time, they are released into the same pool again.
Normal mice can remember and quickly find the platform because they know the location of the platform before, while mice with Alzheimer’s cannot find the platform at the same speed and continue to search. In the second test, the mouse is presented with two objects: one that it has seen before and the other that it has not seen. Normal mice spend more time exploring the new object, but mice with Alzheimer’s cannot remember the difference between the two objects.
Measles is caused by a virus. In most cases, it causes fever and spots on the skin. In rare cases, it can even cause brain damage or death. Under normal circumstances, this virus only infects humans. The reason for this is the two human receptors that allow the virus to bind and enter the cell: CD46 or CD150.
Scientists passed the genes of these receptors into mice to make them susceptible to measles.
After infection, some of these measles mice have been observed to develop severe reactions. For example, in a 2006 article, scientists were able to transform the human CD150 receptor into mice. Later, they infected these mice with measles in two different ways: by injecting the virus into their nostrils or directly into their brains. Most mice began to react rapidly after infection. They lost control of their movements, developed seizures, and died. It was found that the severity of the reactions given depends on the age of the mice. Mortality in newborn mice was 100%, while in mice four weeks old, the mortality rate was 0%. The mortality rate in mice two and three weeks old was between the other two groups.
4) HIV (Human Immunodeficiency Virus)
HIV, which infects millions of people each year, has killed approximately 39 million people to date. HIV infection begins with taking the virus into the cell by special receptors from human cells. Similar to this receptor is also found in chimpanzees, our evolutionary “close cousins.”
Therefore, HIV can also be transmitted to chimpanzees. However, because mice are our much more distant relatives, it is not normally possible to infect mice with HIV. After all, the content of these receptors has changed in the 90 million years since mice and primates diverged. To study this virus on mice in the lab, scientists had to find creative solutions.
The first is to transfer at least three human genes to mice to successfully induce HIV infection. The second and more popular solution is to create mice with human immune systems. To do this successfully, some cells are injected from human to mouse and usually, this procedure includes some surgery. Such mice are called “humanized mice.”
For example, the group of humanized mice called BLT, which takes its name from the Bacon-Lettuce-Tomato (bacon-lettuce-tomato) sandwich, unlike the sandwich, is obtained by transplanting a mixture of human cells from bone marrow, liver, and thymus into mice. To create a BLT mouse, scientists start with a mouse with a compromised immune system.
They then take liver and thymus pieces obtained from human fetuses and transplant them under the kidney of the mouse. They also inject some stem cells derived from human bone marrow. After that, mice called mouse BLT are obtained. These mice have human immune cells and are 100 percent susceptible to HIV. Humanized mice can be infected with HIV through the vagina or anus, or with a needle directly into their veins.
Acne is a skin problem that occurs in humans and causes acne formation. Under normal conditions, a harmless bacterium called Propionibacterium acnes, which is also found in the flora of human skin, begins to attack the skin as the oxygen level in the depths of the skin pores drops. The immune system, which perceives the threat, tries to prevent it from multiplying and turning into a bacterial infection. As a result of this war, pus-filled swelling occurs on the skin, large and small.
Acne occurs neither in our close cousins, chimpanzees nor in mice. So, to study the occurrence of acne, scientists injected mice with this bacterium, called P. acnes, in two ways: ear or back. However, like the bacterium that causes gonorrhea, P. acnes cannot find an environment in the mouse body that can be accommodated. To start this infection in mice, a group of scientists plans to inject human cells into mice.
Human cells are placed in holes drilled in Teflon cylinders and these cylinders are surgically transplanted into the abdomen of mice. One week later the mice are injected with P. acnes. Human cells that manage to survive in the body of mice provide P. acnes to shelter in the mice. In response to this infection, the bodies of mice generate an immune response. With this procedure, acne-like acne formations on the faces of people were successfully obtained to mice.
6) Obsessive-Compulsive Disorder (OCD)
People with obsessive-compulsive disorder (OCD) feel the urge to perform the same action over and over again. While some feel the need to lock the door several times when leaving the house, others wash their hand’s hundreds of times a day. However, there is no such behavior as hand washing in mice. Instead, they engage in an equivalent behavior called “grooming”, where they rub themselves with their paws. Extreme grooming in mice is often used as a model for human OCD.
In many cases of OCD, abnormal activity has been noticed in an area of the brain called the orbitofrontal cortex. To recreate OCD in mice, a group of scientists decided to stimulate the orbitofrontal cortex with a pulse of light. First, they tried a single flash of light but it was not enough to develop OCD. On top of that, they noticed that the mice began to clean and groom themselves more often when they spread the many light pulses over the days.
In the next step, a chemical treatment that has been shown to work in people with OCD was tried on this mouse model and it was discovered that the mice responded to the treatment. Scientists have also managed to get mice with OCD by mutating certain genes. It was observed that some of these mutants had an intense grooming action. For example, the grooming behavior in Hoxb8-mutant mice is so strong that they also pluck their hair. Likewise, Sapap3-mutants rub their faces repeatedly until they hurt.
The intense cravings of alcoholics for alcohol cause them to be physically dependent on alcohol. In some people, alcoholism is genetic, coming from families. As in humans, the “love for alcohol” in mice appears to be genetic. Some species of mice consume very little alcohol, while other species have been observed to drink more. Because mice metabolize alcohol five times faster than humans, they are unlikely to get drunk.
Therefore, to study alcoholism on mice in a laboratory environment, it is necessary to raise mice that love alcohol and consume tons of alcohol voluntarily. To achieve this, scientists select the most alcohol-consuming mice from each generation and breed them among themselves. After continuing this selective breeding for several generations, the latest generation consists of high-alcohol-preferring (HAP) mice.
It was found that when these HAP mice were given water and alcohol at the same time, they preferred to drink alcohol voluntarily, as in humans, and some may get drunk. After hours of drinking, the amount of alcohol in the mice’s blood can rise to three times the legal driving limit. The movements of drunk mice are uncoordinated, so they must struggle to walk on a balance beam.
8) Huntington’s Disease
Huntington’s disease affects people’s nervous system, causing them to gradually lose their ability to control their movements and to think clearly. The huntingtin gene is located on chromosome 4 in humans, and this disease is caused by mutations in this gene. For this reason, Huntington’s disease is genetic. Regular versions of the huntingtin gene contain multiple repeats of CAG, a three-letter DNA sequence. In the disease-causing versions of the gene these repeats get out of control, and there are more than 35 CAG repeats in the mutant Huntingtin gene.
In one experiment, scientists introduced a mutant form containing 72 CAG repeats of the human huntingtin gene into the mice genome. A mouse carrying this 72 repeat gene was found to have problems with motor functions. The same mouse could not complete the beam-crossing test. It was discovered that when he was dropped back on the ground after swinging from his tail, he also had trouble finding a solid place to stand on.
He also tended to walk in circles. As a result of the autopsy, it was discovered that the brain of the mouse began to degenerate, just like the brains of Huntington’s patients. Scientists have succeeded in developing many other species of the Huntington mouse. Some species contain only parts of the mutant gene, while others allow the mutant gene to be secreted only in certain brain cells.
Often, people with autism have trouble interacting with other people. In addition to this, some have repetitive behaviors such as clapping their hands. Many different genes contribute to autism risk. For example, the gene called Cntnap2 plays a role in early brain development. In one experiment, scientists were able to disable the Cntnap2 gene in mice. As a result, it was found that some brain cells could not get where they needed to go, and the levels of cells called interneuron decreased in the brain.
In other words, it has been discovered that in these mutants, brain development is different from normal.
Apart from these developmental and biological differences, the behavior of mice lacking the Cntnap2 gene was also observed to be different from normal. Many of these differences were very similar to the symptoms of human autism. For example, juvenile mutant mice, in addition to having less frequency of communicating than other normal mice, were observed to make fewer “calls for help” when they were separated from their mothers.
Adult mutant mice lacking the Cntnap2 gene are less social than normal mice. It turns out that when normal mice are presented with an empty tube and a tube containing a mouse, they generally prefer to investigate the tube containing the mouse, whereas mice without the Cntnap2 gene show no such preference. Like many people with autism, mice without the Cntnap2 gene have been found to engage in repetitive behavior.
For example, it has been observed that they are repeatedly grooming their asses and themselves, even with such frequency that this repetition puts them at risk of injury. These mice have also been proven to respond to risperidone medication like people with autism, and even the repetitive behaviors of the mice taking the drug are controlled but social problems persist.
Schizophrenia is a mental illness. Hallucinations and delusions are their most common and known symptoms. Less common symptoms include apathy and learning problems. MD neuron, a type of brain cell, is less active in patients with schizophrenia.
To recreate this mental difference in mice, neurons were chemically blocked. Later, when the behavior of the mice was examined, it was discovered that they had trouble getting used to the new set of rules for finding food.
This difficulty can be compared to the kind of learning problems that people with schizophrenia have. Schizophrenia is also a genetic disease. Many different genes are thought to play a role. In a Scottish family, a mutation in a gene called DISC1 is predicted to increase the risk of developing schizophrenia. To examine this link, the scientists inserted a mutant form of DISC1 into mice. It has been observed that the brain develops differently in mice with the mutant DISC1.
Several structures called lateral ventricles have been noticed to be larger than normal, particularly on the left side. Such brain differences are also seen in schizophrenia patients. Mice with the mutant gene also showed other symptoms. Sometimes they have been observed to be more hyperactive. For example, it has been found that when left in an open area, they move more than normal mice. However, at other times, it was found that the mice were more apathetic.
For example, it has been found that when dropped into a water bowl, they fight less than normal rats. These differences in behavior are suspected to be associated with schizophrenia. The most common symptoms of schizophrenia, such as hearing voices or believing that they are a famous historical figure, are somewhat difficult to model on mice. Hypothetically, it is unclear whether a schizophrenic mouse would be designed to exhibit these symptoms, as even if it begins to believe that it is Elvis, it will not be able to tell scientists about it. We may need a human brain for this.