New genetic model for Parkinson's disease

”The course of disease in these mice is strikingly similar to human disease”, says Dr. Lars Olson.

In the mouse model generated by the research team, a gene called TFAM is automatically deleted from the genome in dopamine nerve cells only. Without TFAM, mitochondria cannot function normally. The so called respiratory chain is compromised and energy production decreases severely in the dopamine cells.

The new mice are born healthy from healthy but genetically modified parents and will develop spontaneous disease. Previous studies in the field have been based on researchers delivering neurotoxic substances to kill the dopamine neurons. In the new mice, however, mice develop disease slowly in adulthood, like humans with Parkinson's disease, which may facilitate research aimed at finding novel medical treatments and other therapies.

”We see that the dopamine producing nerve cells in the brain stem slowly degenerate”, says Dr. Nils-Göran Larsson. ”In the microscope we can see that the mitochondria are swollen and that aggregates of a protein, probably alpha-synuclein starts to accumulate in the nerve cell bodies. Inclusions of alpha-synuclein-rich so called Lewy bodies is typical for the human disease.”

The causes of Parkinson's disease have long remained a mystery. Genes and environment are both implicated, but recently there has been an increased focus on the roles of genetic factors. It has been found that mutations in a number of genes can lead directly to disease, while other mutations may be susceptibility factors, so that carriers have an increased risk of becoming ill.

A common denominator for some of the implicated genes is their suggested role for the normal functioning of mitochondria.

”Like patients, the mice can be treated with levo-Dopa, a precursor of the lost substance dopamine”, says Dr. Nils-Göran Larsson. ”The course of the disease, as well as the brain changes in this mouse are more similar to Parkinson's disease than most other models. This supports the notion that genetic risk factors are important.”

”Like in patients, the dopamine nerve cells in the new mouse model die in a specific order”, says Dr. Lars Olson. ”We hope the mouse will help us understand why certain dopamine nerve cells are more sensitive than others, so that we can develop drugs that delay, ore even stop the nerve cell death.”

The project, which is a collaboration between Dr. Nils-Göran Larsson's and Dr. Lars Olson's teams and in which Dr. Staffan Cullheim's team has contributed with electron microscopical analysis, is being published this week as an Early edition in Proceedings of the National Academy of Sciences. Collaborations regarding the new Parkinson mouse are also ongoing with Dr. Barry Hoffer's team at NIDA, NIH.

Media Contact

Katarina Sternudd alfa

More Information:

http://www.ki.se

All latest news from the category: Health and Medicine

This subject area encompasses research and studies in the field of human medicine.

Among the wide-ranging list of topics covered here are anesthesiology, anatomy, surgery, human genetics, hygiene and environmental medicine, internal medicine, neurology, pharmacology, physiology, urology and dental medicine.

Back to home

Comments (0)

Write a comment

Newest articles

New anti-cancer agent works without oxygen

Why tumors shrink but don’t disappear. “As tumors grow very quickly, consume a lot of oxygen and their vascular growth can’t necessarily keep pace, they often contain areas that are…

First blueprint of the human spliceosome revealed

Researchers detail the inner workings of the most complex and intricate molecular machine in human biology. Researchers at the Centre for Genomic Regulation (CRG) in Barcelona have created the first…

A paper-aluminum combo for strong, sustainable packaging

Takeout containers get your favorite noodles from the restaurant to your dining table (or couch) without incident, but they are nearly impossible to recycle if they are made from foil-lined…