The University of Iowa

Annual Report 2010-2011

Out Front logo--The University of Iowa

Muscular dystrophy discovery

UI team identifies new gene mutation that causes the condition

A strong international collaboration and a single patient with mild muscle disease and severe cognitive impairment have allowed University of Iowa researchers to identify a new gene mutation that causes muscular dystrophy.

Furthermore, by engineering the human gene mutation into a mouse, the researchers, led by Kevin Campbell, professor and head of molecular physiology and biophysics at the UI Carver College of Medicine and a Howard Hughes Medical Institute investigator, have created a new mouse model that could help screen potential drugs to treat this type of muscular dystrophy.

The study, published in the March 10, 2011, issue of the New England Journal of Medicine, also ties together almost two decades of research on dystroglycan, an important muscle protein that is abnormal in a group of congenital muscular dystrophies, which often involve brain abnormalities.

Normal dystroglycan protein is extensively modified with added sugar chains. This modification allows dystroglycan to interact with other cellular proteins and by doing so provide structural strength and integrity to cell membranes in many tissues, including muscle and brain.

Several enzymes are involved in adding sugar chains onto the dystroglycan protein, and mutations in these enzymes cause congenital muscular dystrophies collectively known as secondary dystroglycanopathies. In these disorders, too few sugar groups are added to the dystroglycan protein. The resulting dystroglycan does not attach properly to other proteins, leading to muscle and neurological problems.

"In all these muscular dystrophies, the core dystroglycan protein is normal, so there was always the question, 'Did the sugar-adding enzymes act on other proteins as well as dystroglycan, and could those other unknown proteins be important for muscular dystrophy?'" says Campbell, who also is a UI professor of internal medicine and neurology and holds the Roy J. Carver Chair of Molecular Physiology and Biophysics. "Finding a mutation in the dystroglycan protein itself, which produces similar muscle and brain problems as are seen in these 'secondary' muscular dystrophies, suggests that dystroglycan is the major substrate, and probably the only substrate, in these other diseases."

Campbell's team, including UI postdoctoral fellow Yuji Hara, collaborated with colleagues in Turkey, Switzerland, England, New York, and California to study the mutation found in a Turkish patient with a mild muscular dystrophy and severe cognitive impairment.

The team found that all genes for the known sugar-adding enzymes were normal, but there was a single mutation in the gene for the dystroglycan protein. Further analysis showed that the mutated protein did not get its full complement of added sugar molecules, and was not able to interact efficiently with its normal cell partners either in muscle or brain. The researchers showed that the mutation blocked normal interaction between dystroglycan and one of the sugar-adding enzymes, thus disrupting the addition of sugar chains required for dystroglycan to function.

The researchers then engineered the genetic mutation into mouse dystroglycan and found that the animals have muscle and brain abnormalities similar to the Turkish patient and to patients with the secondary dystroglycanopathies. Taken together, the data strongly suggests that the mutation causes neurological problems as well as muscle disease as a consequence of impaired dystroglycan modification.

With the discovery of the mutation in the dystroglycan protein itself, Campbell's team has found an example of a new disease class known as primary dystroglycanopathy.

Although this finding is based on only one patient, Campbell noted that the mutation produced such mild muscle disease, especially compared to the severe cognitive symptoms, that it was not immediately obvious that the patient had a muscular dystrophy.

"This might mean that there are other patients who have not been correctly diagnosed as having a muscular dystrophy because their major symptoms are cognitive rather than muscular," he says. "Sometimes you just need that first patient case for clinicians to recognize that they have patients whose symptoms may also be caused by a particular mutation."

stories about people, being human, our bodies, minds, health care, or existential questions

P also stands for Provost

P. Barry ButlerMason names P. Barry Butler executive vice president and provost...more

Peel appeal

Substance found in apples promotes muscle growth in mice...more

Fear discovery

Fear discovery could lead to new interventions for PTSD...more

Cystic fibrosis finding

UI-led study could help predict severity of disease, may lead to new therapies...more

Locking out Ebola?

UI-led research team identifies receptor for virus...more

Beating mealtime woes

Pediatric feeding program helps children overcome severe eating difficulties...more

Furry FriendsProgram provides emotional lift to young patients...more

a patient hugs a dog that is part of the Furry Friends program

Working toward justice

UI law students help commute abused woman’s prison sentence...more

Body-language bewilderment

UI study investigates variability in men's recall of sexual cues...more

Muscular dystrophy discovery

muscular dystrophy microscopic viewUI team identifies new gene mutation that causes the condition...more

Nursing dedicates center

Top-rated gerontological/geriatric program gets boost from $2.2M donation...more

Heard the buzz?

University of Iowa researchers identify caffeine-consuming bacterium...more

things associated with work—business research, economic development, education

You can’t beat BONGO

BONGO app on a smartphoneNew service helps bus riders get real-time route information via mobile devices...more

Quite the impact

UI contributes $6 billion annually to Iowa economy, creates 1 in 30 jobs...more

Meet the dean

Margaret Crocco, College of Education deanMargaret Crocco leading College of Education...more

Holy hardware!

High-performance computing cluster is UI's largest supercomputer ever...more

A precarious development

UI study finds employee training might actually increase turnover...more

“Transformation, reflection”

dentistry building renderingUI Colleges of Dentistry, Pharmacy celebrate landmark moments...more

Did you see that?

Marketing researcher examines how we remember what we don't remember...more

Taking back the message

hip hop magazine creatorAlum rocks the BELL with hip-hop magazine...more

Meeting real challenges

Wild Bill's Coffee Shop signBusiness student group aids nonprofit organizations... more

Online approach adds up

UI offers new Web-based resources to maximize student math potential...more

Stop the wacky wikis!

wikipedia logoUI researchers design tool to improve Wikipedia accuracy...more

Managers matter

UI researcher finds that bad leadership wrecks companies, despite what leaders wish...more

stories about Iowa, the country, the world, the universe (geography, flooding, immigration, space)

Lightening their load

Virtual Soldier Research helping Navy, Marines with combat effectiveness...more

A welcome proposal

Iowa Flood Center embraces call to develop national flood center...more

Something in the air

UI researcher finds black carbon implicated in global warming...more

Set sail on micro scale

IIHR wave basinIIHR–Hydroscience & Engineering unveils $4.9 million wave basin...more

Sharing our gift

South Korean teachers visit UI to learn more about gifted education...more

Herky hits D.C.Hawkeye Caucus makes trip to nation's capital...more

Herky outside White House in DC

Helping unify a nation

College of Law professor guides Nepal toward new constitution...more

Giving Chile a clearer picture

UI researchers develop system to predict air pollution events for Santiago...more

Screening overseas

Films with UI ties play at renowned Venice, Cannes festivals...more

Aiding a town’s turnaround

Grad students partner with Dubuque on sustainability initiative...more

Beyond science

Lakeside LabLakeside Lab in northwest Iowa serves as regents resource center...more

A global grasp

New UI student group seeks to improve UI, China business opportunities...more

arts and entertainment, athletics

A plan of note

LMN Architects selected to design new facility for UI School of Music...more

Fit for EveryoneNew recreation and wellness center opens...more

Campus Recreation and Wellness Center

Something to admire

UIMA Director Sean O’Harrow envisions art museum for 21st century...more

Hawks’ run continues

Football squad notches third straight bowl win at 2010 Insight Bowl...more

Sophocles, rebooted

University Theatres Mainstage presents interactive Antigone 2.0...more

India has honors

Hawkeye golfer named Big Ten Player of the Year...more

Democracy's harmony

School of Music ensemble’s interactive presentation is music to students’ ears...more

Those Who CanExhibit honors departed art faculty...more

Tom Aprile exhibit

Ladies take KinnickA sporting way to tackle a fund-raiser...more

Marcus Coker hangs on to the ball as a Ladies Football Academy participants tries to take it away

This app is apropos

UI development team launches Iowa City UNESCO City of Literature iPhone app...more

Giving life to the defunct

old typewriterUI literary magazine focuses on trends, fads, cultures that have come and gone...more

More than a game

Law school helps students study the legal side of sports...more

Featured

Renugan Raidoo, Rhodes Scholar

Renugan Raidoo

Five Weeks in Ghana

Five Weeks in Ghana

Strategizing Sustainability

trategizing Sustainability

The Magnificent Milers

The Magnificent Milers

One for the Ages

One for the Ages