Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


UCSF transgenic mouse mimics Parkinson’s earliest symptoms

UCSF researchers have created the first transgenic mouse to display the earliest signs of Parkinson’s disease using the genetic mutation that is known to accompany human forms of the disease.

The mouse model, which expresses the same mutant proteins as human Parkinson’s patients, also displays early signs of constipation and other gastrointestinal problems that are a common harbinger of the disease in humans.

As a result, researchers say, these animals could serve as a means of investigating therapies for reversing the neurological dysfunction of the disease at its earliest stages.

The findings are featured as the cover story in the May 1, 2010 issue of the journal, “Human Molecular Genetics” and are available online at

Researchers have long suspected that the neurological component of Parkinson’s, which causes tremors and stiffness among other symptoms, is actually a late-stage effect of a larger, systemic problem, according to UCSF geneticist Robert L. Nussbaum, MD, who was senior author on the paper.

“This new model validates that theory by mimicking what we know to be the genetic pathway leading to Parkinson’s, while also displaying the earliest symptoms that occur in humans,” said Nussbaum, who is the Holly Smith Distinguished Professor in Medicine and chief of the UCSF Division of Medical Genetics. “This will give us an important tool in identifying an early intervention for this devastating disease.”

Parkinson’s disease is the second most common neurodegenerative disease after Alzheimer’s, affecting 1.5 percent of adults over 55 years of age, and is typically characterized by motor disorders such as tremors, rigidity and postural instability.

Several non-motor abnormalities also frequently accompany Parkinson’s, including depression, sleep disorders and gastrointestinal dysfunction, the researchers explained. Gastrointestinal dysfunction is a particularly common symptom, seen in 80 to 90 percent of patients, and often precedes the motor-control symptoms by 10 to 15 years.

The UCSF mouse model is the first to display the full gastrointestinal symptoms as well, and is consistent with the progression of the disease in humans.

Nussbaum, in collaboration with former colleague Mihael Polymeropoulos, MD, had previously identified the first Mendelian-inherited form of Parkinson’s, which involves a mutation in the gene that produces alpha-synuclein proteins. Since then, he has been studying the rare, inherited forms of the disease to better understand the pathways and processes that may be involved in the more common, sporadic forms, and to create mouse models of the disease that can help in developing therapies.

The current model, based on that research, is significant in having the same genetic mutation that causes alpha-synuclein to misfold in an inherited form of Parkinson’s, causing the proteins to stick together to form insoluble fibrils in the nerve cells. Those clumps, known as Lewy bodies, are often associated with Parkinson’s, as well as with some other forms of dementia and multiple system atrophy.

Previous mouse models of the disease had relied on an over-expression of alpha-synuclein caused by a combination of human and mouse genes, according to the paper. The UCSF team created two new lines that only express the human form of the protein, with each line expressing one of two mutant forms that occur in human Parkinson’s patients, according to lead author Yien-Ming Kuo, PhD, in the UCSF Institute for Human Genetics.

In these lines, gastrointestinal dysfunction could be seen at three months of age, reached its highest severity at six months and persisted until 18 months, which follows the human course of the disease in sporadic Parkinson’s, according to the paper. That dysfunction occurred before there was any evidence of loss of smell and also before any evidence arose of pathological changes in the brain stem.

“This suggests that, at least in mice with the human proteins, these gastrointestinal symptoms are an intrinsic defect caused by the mutant protein, rather than being caused by abnormalities in brain function,” Kuo said. “That knowledge could eventually help us test for the disease long before it starts to cause neurodegenerative problems and prevent them from occurring.”

The work was funded by the National Institutes of Health, a grant from the Michael J. Fox Foundation, institutional funding from the UCSF Department of Medicine and Institute of Human Genetics, and the American Lebanese Syrian Associated Charities. The authors report no conflicts of interest on this research.

Co-authors on the paper include Zhishan Li and Michael D. Gershon, from the Department of Pathology and Cell Biology, Columbia University, New York, NY; Yun Jiao, Amar K. Pani and Richard J. Smeyne, of the Department of Developmental Neurobiology, St. Jude Children’s Research Hospital, Memphis, TN; Nathalie Gaborit and Benoit G. Bruneau, of the Gladstone Institute of Cardiovascular Disease, San Francisco, CA; Bonnie M. Orrison of the Genetic Disease Research Branch, National Institutes of Health, Bethesda, MD; and Benoit I. Giasson, of the Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA.

UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. For further information, visit

Kristen Bole | EurekAlert!
Further information:

More articles from Life Sciences:

nachricht Novel mechanisms of action discovered for the skin cancer medication Imiquimod
21.10.2016 | Technische Universität München

nachricht Second research flight into zero gravity
21.10.2016 | Universität Zürich

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

Im Focus: New Products - Highlights of COMPAMED 2016

COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.

In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...

Im Focus: Ultra-thin ferroelectric material for next-generation electronics

'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.

Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Resolving the mystery of preeclampsia

21.10.2016 | Health and Medicine

Stanford researchers create new special-purpose computer that may someday save us billions

21.10.2016 | Information Technology

From ancient fossils to future cars

21.10.2016 | Materials Sciences

More VideoLinks >>>