Interview with Francisco Perez about the knockout mice project.

Francisco Perez is a Graduate Student in the Neurobiology and Behavior Program at the University of Washington in Seattle

A Parkinson’s knockout mouse model developed by researchers at the UW Health Sciences could bring good news to the future generation.

Questions by Tatiana Chernih

Answered by Francisco Perez

Q: Please describe what your project is about.

A: Parkinson’s disease is an age-related neurodegenerative disorder that affects more than 1 million Americans. Although it is known that the loss of specific neurons in the brain leads to the characteristic symptoms of Parkinson’s, it is not known how or why these neurons die. I am interested in understanding how and why these neurons degenerate with the hope of developing treatments to prevent it.

Recently, a significant advancement in the understanding of Parkinson’s was made when researchers in Japan discovered that mutations in a gene called “parkin” can lead to a heritable form of Parkinson’s. It is thought that the protein encoded by this gene may normally keep neurons healthy and prevent them from degenerating. When there are mutations in critical regions of the parkin gene, the potentially protective protein is not made or does not function properly leading to neurodegeneration.

My specific interest is in understanding how mutations in the parkin gene lead to Parkinson’s disease. We are addressing this question using a mouse in which the parkin gene was “knocked out.” In other words, these mice have mutations in the parkin gene that are similar to those found in humans with a heritable form of Parkinson’s. We expect these mice to develop a neurodegenerative disease similar to Parkinson’s. These mice will be extremely helpful for understanding how and why neurons degenerate in Parkinson’s and for developing new treatments for Parkinson’s.

Q: Are there problems that you may encounter in this process?

A: There are several potential problems that face us. One of them is the short lifespan of mice which live for about 2-3 years. In humans, however, Parkinson’s typically develops after more than 50 years. Thus, these lifespan differences could be problematic. It is possible that mice don’t live long enough to develop a disease similar to Parkinson’s. On the other hand, the aging process in mice is thought to be similar to that of humans so it doesn’t seem unlikely to expect Parkinson’s in a mouse after 1-2 years. Another potential problem is that mice may have developed ways to compensate when there is no parkin protein. In other words, mice may not develop Parkinson’s when parkin is missing because they may have backup systems not found in humans that protect against neurodegeneration. If this turns out to be the case, it would be very interesting to study these protective mechanisms in the mouse to help develop new Parkinson’s treatments.

Q: Is the use of an animal model necessary?

A: In order to understand how and why neurons degenerate in Parkinson’s it is crucial to have an appropriate and relevant animal model. One of the limiting steps in Parkinson’s disease research is the availability of models to study this disease. An animal model enables researchers to understand the mechanism of disease in a complex organism. By understanding the mechanism, these models can be used to develop and investigate new treatments. Moreover, animal models can be used to identify changes that occur in an organism before disease develops. Understanding these changes will lead to advancements in early diagnosis and prevention of Parkinson’s.

Q: What is the downside of using mice as a model for studying Parkinson’s disease?

A: Although studies using transgenic and knockout mice have significantly advanced our understanding of human disease, things don’t always work the same way in mice as they do in humans. Although humans with mutations in the parkin gene develop Parkinson’s disease, there is no guarantee that mice with similar mutations will also develop the disease due to the limitations I described before.

Q: What do you think about stem cell treatment for Parkinson’s?

A: Stem cells are a promising option for replacing the neurons that degenerate in Parkinson’s. However, my hope is that we will find a way to identify people at risk for developing Parkinson’s and prevent the neurons from degenerating in the first place.

Q: Anything else you would like to add, Mr. Perez?

A: Hopefully this Parkinson’s model will be useful for understanding how and why neurons degenerate in this disease so we can develop treatments to prevent the neurodegeneration. It is also likely that advancing our understanding of Parkinson’s disease will lead to a greater understanding of other neurodegenerative disorders, such as Alzheimer’s and ALS, that are thought to share a similar mechanism.

Thank you very much for sharing with us your ideas.

You are welcome.