Featured Research

from universities, journals, and other organizations

Nerve Disorder In Mice And Men Linked To Mutated Gene

Date:
October 13, 2003
Source:
University Of Michigan Health System
Summary:
In a discovery that reinforces the importance of the mouse to human genetics, scientists at the University of Michigan Medical School have discovered two mutations in a gene called ATCAY, which appear to be responsible for Cayman ataxia in humans and for similar neurological disorders in mice.

ANN ARBOR, MI – In a small town on Grand Cayman Island in the Caribbean, people are living with a serious neurological disorder, called Cayman ataxia, found nowhere else in the world.

Related Articles


People born with this rare, inherited condition have poor muscle coordination, some degree of mental retardation, uncontrollable head and eye movements and difficulty speaking or walking.

Now, in a discovery that reinforces the importance of the mouse to human genetics, scientists at the University of Michigan Medical School have discovered two mutations in a gene called ATCAY, which appear to be responsible for Cayman ataxia in humans and for similar neurological disorders in mice.

Cayman ataxia is one of about 100 rare inherited neurological disorders with symptoms that include ataxia, according to Margit Burmeister, Ph.D., a senior associate research scientist at the U-M Mental Health Research Institute and an associate professor of psychiatry and of human genetics in the University of Michigan Medical School. While the severity of symptoms can vary, people with ataxia have limited or no control over posture or coordination of their arms and legs.

"Because these disorders are so rare, it is difficult to collect DNA samples from enough affected individuals in different families with the same disorder to pinpoint the mutations that cause them," Burmeiser says. "Unless we can identify the mutated gene, it's hard to develop a diagnostic test or a therapy to help people with the disease."

A paper describing the research study will be published online October 12 by Nature Genetics, and will appear in the November issue of the journal. It is the result of a collaboration between scientists at the University of Michigan, the University of Miami, the University of Iowa and the National Human Genome Center at Howard University.

Before the U-M study, scientists knew that Cayman ataxia was caused by a recessive mutant gene originating in one of the early residents of Grand Cayman Island and passed on through the generations by his or her descendants. In 1994, scientists at the University of Iowa narrowed the search to one region on human chromosome 19, which included 50 to 100 genes, but couldn't locate the specific gene responsible for the disorder.

Meanwhile, Burmeister was working with a strain of mutant mice, called "jittery", with similar neurological symptoms, but so severe that affected mice die a few weeks after birth. She wondered if the gene that caused the disorder in mice could be the same gene responsible for Cayman ataxia in humans. So she compared overlapping DNA sequences between the region on mouse chromosome 10 defined by the "jittery" mice and the region on human chromosome 19 implicated in Cayman ataxia.

"Comparing overlapping DNA sequences between human and mouse narrowed the interval down to a much smaller region that contained just seven genes," Burmeister says. "In one of these genes, we discovered two mutations – a recessive mutation that caused lethal ataxia in "jittery" mice and another mutation that caused milder symptoms in a different strain of mice called "hesitant".

Burmeister then analyzed anonymous DNA samples, provided by University of Iowa scientists, from Cayman Island residents with ataxia and from relatives who did not have the disorder. When they sequenced human DNA, U-M scientists found the same two mutations in the same gene, which they named ATCAY, for Ataxia, Cayman type. Both mutations were present in every patient with Cayman ataxia in the study. Neither mutation was found in 1,000 control chromosomes from people of European, Jamaican or African ancestry.

"One of the mutations in the ATCAY gene changes an amino acid and the other is a splice mutation expressing a non-functional, truncated form of caytaxin, the protein expressed by the gene," Burmeister explains.

When U-M scientists analyzed gene expression in tissue from mice in the study, they found caytaxin protein was present throughout the brain and in neurons, but nowhere else in the mouse's body.

"We don't know what this protein does, but it doesn't appear to affect the physical development or structure of the brain or nervous system in mice, which appeared completely normal," Burmeister says. "Unlike other ataxias, there were no neurodegenerative changes."

According to Burmeister, the DNA sequence encoding caytaxin protein is somewhat similar to that of a Vitamin-E transporting protein, which is involved in another rare form of ataxia. People with this form of ataxia respond well to treatment with large doses of Vitamin E. But Vitamin E does not seem to bind to caytaxin, so the same treatment would not help people with Cayman ataxia.

Currently, Burmeister is working with structural biologists to determine what molecules will fit into the binding pocket of the caytaxin protein.

"If we can determine caytaxin's function, that will tell us why these people have ataxia, which would be a major step toward finding ways to prevent or treat the disorder," Burmeister says.

She also plans additional research to see whether mutations in ATCAY could be responsible for other types of inherited ataxia.

###

The University of Michigan has filed two provisional patent applications on the ataxia-associated gene and its protein. The research was funded by the National Institutes of Health, the March of Dimes Birth Defect Foundation, and the government of the Cayman Islands.

Jamee Bomar, a U-M research assistant, was first author on the paper. Other co-authors from U-M included Roger Albin, M.D., U-M professor of neurology; Paresh Patel, M.D., Ph.D., U-M assistant professor of psychiatry; undergraduates Eric Slattery and Radhika Puttagunta; Larry Taylor, Ph.D, research associate; and Eunju Seong, a graudate student in neuroscience. Co-authors Arne Nystuen and Val C. Sheffield are from the University of Iowa Medical School. Co-authors Rick Kittles and Weidong Chen are from the National Human Genome Center at Howard University. Co-author Paul J. Benke, from the University of Miami Medical School, did the original clinical research on individuals with Cayman ataxia.

Nature Genetics (2003), November 2003.


Story Source:

The above story is based on materials provided by University Of Michigan Health System. Note: Materials may be edited for content and length.


Cite This Page:

University Of Michigan Health System. "Nerve Disorder In Mice And Men Linked To Mutated Gene." ScienceDaily. ScienceDaily, 13 October 2003. <www.sciencedaily.com/releases/2003/10/031012233900.htm>.
University Of Michigan Health System. (2003, October 13). Nerve Disorder In Mice And Men Linked To Mutated Gene. ScienceDaily. Retrieved December 21, 2014 from www.sciencedaily.com/releases/2003/10/031012233900.htm
University Of Michigan Health System. "Nerve Disorder In Mice And Men Linked To Mutated Gene." ScienceDaily. www.sciencedaily.com/releases/2003/10/031012233900.htm (accessed December 21, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Sunday, December 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

The Best Tips to Curb Holiday Carbs

The Best Tips to Curb Holiday Carbs

Buzz60 (Dec. 19, 2014) It's hard to resist those delicious but fattening carbs we all crave during the winter months, but there are some ways to stay satisfied without consuming the extra calories. Vanessa Freeman (@VanessaFreeTV) has the details. Video provided by Buzz60
Powered by NewsLook.com
Sierra Leone Bikers Spread the Message to Fight Ebola

Sierra Leone Bikers Spread the Message to Fight Ebola

AFP (Dec. 19, 2014) More than 100 motorcyclists hit the road to spread awareness messages about Ebola. Nearly 7,000 people have now died from the virus, almost all of them in west Africa, according to the World Health Organization. Video provided by AFP
Powered by NewsLook.com
Researchers Test Colombian Village With High Alzheimer's Rates

Researchers Test Colombian Village With High Alzheimer's Rates

AFP (Dec. 19, 2014) In Yarumal, a village in N. Colombia, Alzheimer's has ravaged a disproportionately large number of families. A genetic "curse" that may pave the way for research on how to treat the disease that claims a new victim every four seconds. Duration: 02:42 Video provided by AFP
Powered by NewsLook.com
The Best Protein-Filled Foods to Energize You for the New Year

The Best Protein-Filled Foods to Energize You for the New Year

Buzz60 (Dec. 19, 2014) The new year is coming and nothing will energize you more for 2015 than protein-filled foods. Fitness and nutrition expert John Basedow (@JohnBasedow) gives his favorite high protein foods that will help you build muscle, lose fat and have endless energy. Video provided by Buzz60
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