Featured Research

from universities, journals, and other organizations

Scientists Develop Transgenic Mouse That Models Parkinson's, Related Disorders

Date:
February 21, 2000
Source:
University Of California, San Diego
Summary:
The first mouse model genetically programmed to simulate motor deficits and brain alterations found in Parkinson’s disease and related disorders has been developed by a team of scientists at the University of California, San Diego; the University of California, San Francisco, and the Gladstone Institute of Neurological Disease.

The first mouse model genetically programmed to simulate motor deficits and brain alterations found in Parkinson’s disease and related disorders has been developed by a team of scientists at the University of California, San Diego; the University of California, San Francisco, and the Gladstone Institute of Neurological Disease. The research was led by Eliezer Masliah, M.D., of the UCSD Departments of Neurosciences and Pathology.

The investigators report in the Feb. 18 issue of Science that mice bred to express a human protein called alpha-synuclein in the brain develop protein deposits in specific brain regions associated with Parkinson’s disease, and also have impaired motor function.

"Previous studies have shown increased levels of this protein in the brain cells of Parkinson’s patients, but whether they were a cause or result of the disease has not been clear," said Masliah. "With these results we have demonstrated that alpha-synuclein is in fact involved in the onset of diseases such as Parkinson’s. The development of symptoms in these genetically altered mice resembles disease progression in humans. This gives us a new model for studying Parkinson’s disease and related disorders such as Alzheimer’s disease."

The overexpression of alpha-synuclein in the brain cells of the mice is consistent with the accumulation of this protein in Parkinson’s patients. Alzheimer’s disease is also characterized by an abnormal accumulation of proteins in neurons, and Alzheimer’s and Parkinson’s disease frequently overlap.

"For many of the chemical and pathological changes one finds in brain diseases, it is hard to tell if they are a cause or consequence of the disease," said study co-author Lennart Mucke, M.D., Professor of Neurology and Neuroscience at UCSF and Director of the Gladstone Institute of Neurological Disease in San Francisco. "Our findings in experimental models demonstrate for the first time that accumulation of human alpha-synuclien in neurons actually causes a number of alterations found in these human disorders, namely, an abnormal build-up of proteins in brain cells, a loss of specific neuronal connections, and impairments of motor skills. These results suggest that blocking the accumulation of alpha-synuclein might help prevent or treat Parkinson’s and related conditions."

In this study, the human gene for alpha-synuclein was inserted into fertilized mouse egg cells. The eggs were then implanted into mice, which produced offspring expressing the gene in neurons. Among the offspring were animals with high levels of protein in the brain; these animals have been used to develop a colony of transgenic mice that consistently develop brain pathology and symptoms resembling those in patients with Parkinson’s disease.

Parkinson’s disease results from the degeneration of specific brain cells that regulate the activity of other brain cells by releasing a chemical called dopamine.

"Previous models for Parkinson’s disease in mice have been achieved through chemical or surgical techniques that interfere with the dopaminergic system, but it is unclear whether these interventions simulate what triggers the disease in people," said Masliah.

In this model, a protein that is known to accumulate in humans with Parkinson’s disease predisposes the mice to the age-related degeneration of dopaminergic connections between brain cells, and to the development of motor deficits, the investigators say. This model sheds light on the role of alpha-synuclein in neurodegenerative disorders and will be useful in the development and testing of new drugs for these conditions, they add.

The study’s co-authors also include Edward Rockenstein, Margaret Mallory, Makoto Hashimoto, Isaac Veinbergs, Yutaka Sagara, Abbyanne Sisk and Ayako Takeda of the UCSD Department of Neurosciences.

The research was supported by the National Institute on Aging, The J. David Gladstone Institutes and the Spencer Family Foundation.


Story Source:

The above story is based on materials provided by University Of California, San Diego. Note: Materials may be edited for content and length.


Cite This Page:

University Of California, San Diego. "Scientists Develop Transgenic Mouse That Models Parkinson's, Related Disorders." ScienceDaily. ScienceDaily, 21 February 2000. <www.sciencedaily.com/releases/2000/02/000218054728.htm>.
University Of California, San Diego. (2000, February 21). Scientists Develop Transgenic Mouse That Models Parkinson's, Related Disorders. ScienceDaily. Retrieved September 3, 2014 from www.sciencedaily.com/releases/2000/02/000218054728.htm
University Of California, San Diego. "Scientists Develop Transgenic Mouse That Models Parkinson's, Related Disorders." ScienceDaily. www.sciencedaily.com/releases/2000/02/000218054728.htm (accessed September 3, 2014).

Share This



More Health & Medicine News

Wednesday, September 3, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Snack Attack: Study Says Action Movies Make You Snack More

Snack Attack: Study Says Action Movies Make You Snack More

Newsy (Sep. 2, 2014) You're more likely to gain weight while watching action flicks than you are watching other types of programming, says a new study published in JAMA. Video provided by Newsy
Powered by NewsLook.com
U.N. Says Ebola Travel Restrictions Will Cause Food Shortage

U.N. Says Ebola Travel Restrictions Will Cause Food Shortage

Newsy (Sep. 2, 2014) The U.N. says the problem is two-fold — quarantine zones and travel restrictions are limiting the movement of both people and food. Video provided by Newsy
Powered by NewsLook.com
Doctors Fear They're Losing Battle Against Ebola

Doctors Fear They're Losing Battle Against Ebola

AP (Sep. 2, 2014) As a third American missionary is confirmed to have contracted Ebola in Liberia, doctors on the ground in West Africa fear they're losing the battle against the outbreak. (Sept. 2) Video provided by AP
Powered by NewsLook.com
Tech Giants Bet on 3D Headsets for Gaming, Healthcare

Tech Giants Bet on 3D Headsets for Gaming, Healthcare

AFP (Sep. 2, 2014) When Facebook acquired the virtual reality hardware developer Oculus VR in March for $2 billion, CEO Mark Zuckerberg hailed the firm's technology as "a new communication platform." Duration: 02:24 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins