Featured Research

from universities, journals, and other organizations

Mouse Model Of Prion Disease Mimics Diverse Symptoms Of Human Disorder

Date:
November 28, 2008
Source:
Cell Press
Summary:
A comprehensive mouse model of inherited prion disease exhibits cognitive, motor and neurophysiological deficits that bear a striking resemblance to the symptoms experienced by patients with the human version of "mad cow disease," Creutzfeldt-Jakob disease. The research, published in the journal Neuron, provides exciting insight into the mechanism of disease and may lead to the development of new therapeutic strategies for this devastating neurodegenerative disorder.

A comprehensive mouse model of inherited prion disease exhibits cognitive, motor, and neurophysiological deficits that bear a striking resemblance to the symptoms experienced by patients with the human version of "mad cow disease," Creutzfeldt-Jakob disease (CJD). The research, published by Cell Press in the November 26th issue of the journal Neuron, provides exciting insight into the mechanism of disease and may lead to the development of new therapeutic strategies for this devastating neurodegenerative disorder.

Mutation in the D178N/V129 prion protein (PrP) is associated with a subtype of CJD characterized by early cognitive impairment with memory deterioration, behavioral and motor abnormalities, electroencephalographic (EEG) changes, and specific neuropathological alterations. To date, only two transgenic models of inherited prion disease exist, which develop motor deficits but do not recapitulate the cognitive and neurophysiological abnormalities typical of CJD.

"We need experimental models with a broader spectrum of clinical signs for insight into the mechanisms of neuronal dysfunction and its evolution, and to identify earlier markers of clinical disease when therapeutic intervention may be effective," says senior study author Dr. Roberto Chiesa of the "Mario Negri" Institute for Pharmacological Research in Milan, Italy. Dr. Chiesa and colleagues developed a new transgenic mouse model of CJD expressing the mouse homolog of the D178N/V129 mutation.

The mice, called Tg(CJD) mice, show motor symptoms, but also memory impairment and neurophysiological deficits, specifically EEG abnormalities and sleep alterations, strikingly similar to those observed in a CJD patient with the same mutation. The researchers also observed several neuropathological abnormalities in the Tg(CJD) mice, including alterations in the endoplasmic reticulum (ER), the neuronal protein trafficking machinery, and an associated intracellular retention of mutant PrP. This suggests that ER dysfunction might contribute to CJD pathology.

These findings demonstrate that Tg(CJD) mice faithfully mirror clinical and pathological symptoms associated with CJD. "Our results establish the first animal model of a genetic prion disease recapitulating cognitive, motor, and neurophysiological abnormalities of the human disorder," explains Dr. Chiesa. "This new model allows in-depth analysis of the disease mechanisms and may be useful for testing potential therapies for inherited prion diseases."

The researchers include Sara Dossena, Dulbecco Telethon Institute, Milan, Italy, "Mario Negri" Institute for Pharmacological Research, Milan, Italy; Luca Imeri, University of Milan Medical School, Milan, Italy; Michela Mangieri, Anna Garofoli, Dulbecco Telethon Institute, Milan, Italy, "Mario Negri" Institute for Pharmacological Research, Milan, Italy; Loris Ferrari, Dulbecco Telethon Institute, Milan, Italy, University of Milan Medical School, Milan, Italy; Assunta Senatore, Dulbecco Telethon Institute, Milan, Italy, "Mario Negri" Institute for Pharmacological Research, Milan, Italy; Elena Restelli, Dulbecco Telethon Institute, Milan, Italy, "Mario Negri" Institute for Pharmacological Research, Milan, Italy; Claudia Balducci, "Mario Negri" Institute for Pharmacological Research, Milan, Italy; Fabio Fiordaliso, "Mario Negri" Institute for Pharmacological Research, Milan, Italy; Monica Salio, "Mario Negri" Institute for Pharmacological Research, Milan, Italy; Susanna Bianchi, University of Milan Medical School, Milan, Italy; Luana Fioriti, Dulbecco Telethon Institute, Milan, Italy, "Mario Negri" Institute for Pharmacological Research, Milan, Italy; Michela Morbin, "Carlo Besta" National Neurological Institute, Milan, Italy; Alessandro Pincherle, "Carlo Besta" National Neurological Institute, Milan, Italy; Gabriella Marcon, "Carlo Besta" National Neurological Institute, Milan, Italy, University of Udine, Udine, Italy; Flavio Villani, "Carlo Besta" National Neurological Institute, Milan, Italy; Mirjana Carli, "Mario Negri" Institute for Pharmacological Research, Milan, Italy; Fabrizio Tagliavini, "Carlo Besta" National Neurological Institute, Milan, Italy; Gianluigi Forloni, "Mario Negri" Institute for Pharmacological Research, Milan, Italy; and Roberto Chiesa, Dulbecco Telethon Institute, Milan, Italy, "Mario Negri" Institute for Pharmacological Research, Milan, Italy.


Story Source:

The above story is based on materials provided by Cell Press. Note: Materials may be edited for content and length.


Cite This Page:

Cell Press. "Mouse Model Of Prion Disease Mimics Diverse Symptoms Of Human Disorder." ScienceDaily. ScienceDaily, 28 November 2008. <www.sciencedaily.com/releases/2008/11/081126133300.htm>.
Cell Press. (2008, November 28). Mouse Model Of Prion Disease Mimics Diverse Symptoms Of Human Disorder. ScienceDaily. Retrieved July 30, 2014 from www.sciencedaily.com/releases/2008/11/081126133300.htm
Cell Press. "Mouse Model Of Prion Disease Mimics Diverse Symptoms Of Human Disorder." ScienceDaily. www.sciencedaily.com/releases/2008/11/081126133300.htm (accessed July 30, 2014).

Share This




More Mind & Brain News

Wednesday, July 30, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

It's Not Just Facebook: OKCupid Experiments With Users Too

It's Not Just Facebook: OKCupid Experiments With Users Too

Newsy (July 29, 2014) If you've been looking for love online, there's a chance somebody has been looking at how you're looking. Video provided by Newsy
Powered by NewsLook.com
How Your Face Can Leave A Good Or Bad First Impression

How Your Face Can Leave A Good Or Bad First Impression

Newsy (July 29, 2014) Researchers have found certain facial features can make us seem more attractive or trustworthy. Video provided by Newsy
Powered by NewsLook.com
Losing Sleep Leaves You Vulnerable To 'False Memories'

Losing Sleep Leaves You Vulnerable To 'False Memories'

Newsy (July 27, 2014) A new study shows sleep deprivation can make it harder for people to remember specific details of an event. Video provided by Newsy
Powered by NewsLook.com
University Quiz Implies Atheists Are Smarter Than Christians

University Quiz Implies Atheists Are Smarter Than Christians

Newsy (July 25, 2014) An online quiz from a required course at Ohio State is making waves for suggesting atheists are inherently smarter than Christians. Video provided by Newsy
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