Featured Research

from universities, journals, and other organizations

Clinical phenotype similarity in megalencephalic leukoencephalopathy patients explained by zebrafish model study

Date:
June 2, 2014
Source:
Universidad de Barcelona
Summary:
Megalencephalic leukoencephalopathy (MLC) is a genetic neurodegenerative disorder affecting the myelin. Despite research, finer details of the disorder remain quite unknown. To date, there is not any treatment for patients. This rare disease is caused by mutations in MLC1 and GlialCAM and produces megalencephaly, spasticity and ataxia in humans. A new study describes a phenotype of this human disease through the study of genetically-modified zebrafish models.

The experts Alejandro Barrallo and Raúl Estévez, from the Department of Physiological Sciences II at the University of Barcelona.
Credit: Image courtesy of Universidad de Barcelona

Megalencephalic leukoencephalopathy (MLC) is a genetic neurodegenerative disorder affecting the myelin that remains quite unknown. To date, there is not any treatment for patients. This rare disease is caused by mutations in MLC1 and GlialCAM and produces megalencephaly, spasticity and ataxia in humans. A new study of the University of Barcelona, published in the journal Human Molecular Genetics, first describes a phenotype of this human disease through the study of genetically-modified zebrafish models.

Related Articles


The article is signed by Raúl Estévez, Sňnia Sirisi and Alejandro Barrallo, from the Department of Physiological Sciences II on the Bellvitge Health Sciences Campus at the University of Barcelona (UB) and members of the Centre for Biomedical Network Research on Rare Diseases (CIBERER); and Virginia Nunes, lecturer of Genetics at UB, researcher at the Bellvitge Biomedical Research Centre (IDIBELL) and member of CIBERER, among other experts.

Raúl Estévez explains that "patients with recessive mutations in either MLC1 or GLIALCAM show the same clinical phenotype." "However, it is known that gene GlialCAM regulates the activity of two proteins, MLC1 and the chloride channel ClC-2. Therefore, the absence of the gene GlialCAM should produce a severer phenotype than the lack of MLC1."

In order to understand this contradiction, the research group led by Raúl Estévez and Alejandro Barrallo compared genetically-modified zebrafish and mice models -- in other words, knock-out organisms that, in this case, do not express the gene MLC1 -- with the brain biopsy from an MLC patient.

Conclusions state that the lack of MLC1 expression causes the delocalization of protein GlialCAM which mimics neuronal activity in all studied models. Genetic modification in zebrafish models is cheap and easy, so authors point out that future research on these animal models will contribute to understand the molecular relationship that exists between the proteins involved in the physiopathology of megalencephalic leukoencephalopathy.

The article is signed by Raúl Estévez, Sňnia Sirisi and Alejandro Barrallo, from the Department of Physiological Sciences II on the Bellvitge Health Sciences Campus at the University of Barcelona (UB) and members of the Centre for Biomedical Network Research on Rare Diseases (CIBERER); and Virginia Nunes, lecturer of Genetics at UB, researcher at the Bellvitge Biomedical Research Centre (IDIBELL) and member of CIBERER, among other experts.

Raúl Estévez explains that "patients with recessive mutations in either MLC1 or GLIALCAM show the same clinical phenotype." "However, it is known that gene GlialCAM regulates the activity of two proteins, MLC1 and the chloride channel ClC-2. Therefore, the absence of the gene GlialCAM should produce a severer phenotype than the lack of MLC1."

In order to understand this contradiction, the research group led by Raúl Estévez and Alejandro Barrallo compared genetically-modified zebrafish and mice models -- in other words, knock-out organisms that, in this case, do not express the gene MLC1 -- with the brain biopsy from an MLC patient.

Conclusions state that the lack of MLC1 expression causes the delocalization of protein GlialCAM which mimics neuronal activity in all studied models. Genetic modification in zebrafish models is cheap and easy, so authors point out that future research on these animal models will contribute to understand the molecular relationship that exists between the proteins involved in the physiopathology of megalencephalic leukoencephalopathy.


Story Source:

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


Journal Reference:

  1. S. Sirisi, M. Folgueira, T. Lopez-Hernandez, L. Minieri, C. Perez-Rius, H. Gaitan-Penas, J. Zang, A. Martinez, X. Capdevila-Nortes, P. De La Villa, U. Roy, A. Alia, S. Neuhauss, S. Ferroni, V. Nunes, R. Estevez, A. Barrallo-Gimeno. Megalencephalic leukoencephalopathy with subcortical cysts protein 1 regulates glial surface localization of GLIALCAM from fish to humans. Human Molecular Genetics, 2014; DOI: 10.1093/hmg/ddu231

Cite This Page:

Universidad de Barcelona. "Clinical phenotype similarity in megalencephalic leukoencephalopathy patients explained by zebrafish model study." ScienceDaily. ScienceDaily, 2 June 2014. <www.sciencedaily.com/releases/2014/06/140602101405.htm>.
Universidad de Barcelona. (2014, June 2). Clinical phenotype similarity in megalencephalic leukoencephalopathy patients explained by zebrafish model study. ScienceDaily. Retrieved November 20, 2014 from www.sciencedaily.com/releases/2014/06/140602101405.htm
Universidad de Barcelona. "Clinical phenotype similarity in megalencephalic leukoencephalopathy patients explained by zebrafish model study." ScienceDaily. www.sciencedaily.com/releases/2014/06/140602101405.htm (accessed November 20, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Thursday, November 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

UN Says It Will Scale Up Its Ebola Response

UN Says It Will Scale Up Its Ebola Response

AFP (Nov. 20, 2014) — UN Resident Coordinator David McLachlan-Karr and WHO representative in the country Daniel Kertesz updated the media on the UN Ebola response on Wednesday. Duration: 00:51 Video provided by AFP
Powered by NewsLook.com
Takata Offers "sincerest Condolences" To Victims of Malfunctioning Airbag

Takata Offers "sincerest Condolences" To Victims of Malfunctioning Airbag

Reuters - US Online Video (Nov. 20, 2014) — U.S. Congress hears from a victim and company officials as it holds a hearing on the safety of Takata airbags after reports of injuries. Rough Cut (no reporter narration). Video provided by Reuters
Powered by NewsLook.com
Obesity Costs Almost As Much As War And Terrorism

Obesity Costs Almost As Much As War And Terrorism

Newsy (Nov. 20, 2014) — The newest estimate of the cost of obesity is pretty jarring — $2 trillion. But how did researchers get to that number? Video provided by Newsy
Powered by NewsLook.com
Ebola Crisis Affecting US Adoptions

Ebola Crisis Affecting US Adoptions

AP (Nov. 20, 2014) — The Sanborn family had hoped they'd be able to bring home their 5-year-old adopted son from Liberia by now. But Ebola has forced them to wait. The boy is just one of thousands of orphans in West Africa who've been impacted by the deadly virus. (Nov. 20) Video provided by AP
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:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

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