Public Affairs
Baylor College
of Medicine
One Baylor Plaza,
Room 176B
Houston, TX 77030
Telephone:
  (713) 798-4712
Fax:
  (713) 798-3692
email: pa@bcm.tmc.edu

Photos Available Upon Request

Comments, Suggestions?

Gene glitch in Angelman Syndrome identified

By Anissa Anderson Orr

David Sweatt, PhD

The happy disposition that is a hallmark of Angelman Syndrome masks serious problems deep inside the brain. Angelman children cannot learn normally and have particular difficulty with spoken language.

Using a genetically engineered mouse developed at Baylor College of Medicine, researchers have discovered a glitch that might prevent Angelman patients from developing long-term memory. The discovery was published in the April 1 issue of the Journal of Neuroscience.

“We have found a very specific deficit in the hippocampus of the brain in the Angelman mouse in terms of higher learning,” said David Sweatt, PhD, a professor of neuroscience at Baylor. “Having a mouse model allowed us to conduct much more detailed experiments than we could previously and also helped us figure out what was going wrong in the brains of Angelman kids.”

The mouse model carrying a defect in the gene believed to cause Angelman Syndrome was developed at Baylor in 1998 in the lab of Arthur Beaudet, MD, a professor of molecular and human genetics at Baylor. Sweatt’s research into Angelman was a natural next step since his lab uses mouse models to investigate learning and memory.

“One of the interesting things we found in our post-mortem studies of the mouse was that the hippocampus appeared relatively undamaged,” Sweatt said. “One would assume that since this gene is selectively missing from the hippocampus, the brain wouldn’t be wired correctly. But in fact, it looks normal.

“So that meant the deficit had to be much more subtle somehow,” Sweatt continued. “That’s where we come in to look at the physiology and the biochemistry of the hippocampus in the Angelman mouse model.”

Located near the base of the brain, the hippocampus functions as a memory bank. Scientists hypothesize that memory is formed through a process called long-term potentiation (LTP). LTP occurs when the strength of the connection between nerve cells changes. Sustained changes form memories.

To test these connections, Sweatt and his colleagues stimulated the brain tissue of the Angelman mice compared to a group of control mice. They found that the Angelman mice did not have sustained change in nerve connections like the control group. Analyzing the tissue further, they found that it lacked normal amounts of a chemical called calcium/calmodulin-dependent protein kinase II (CaMKII), which regulates LTP.

“Our findings tell us that Angelman syndrome in mice and humans appear to be moderated by a molecular and physiological deficit,” Sweatt said. “Basic scientists have been studying CaMKII for years without knowing it would one day be relevant to human disease.”

The discovery gives researchers more information about what causes the rare, but profoundly disabling disease in humans. But developing a treatment based on this knowledge still lies far in the future.

“We are still missing the 'black box' that links Angelman Syndrome to the molecular and physiological changes that cause the disruption of the CAM kinase,” Sweatt said.

© Copyright 2003 Baylor College of Medicine. All Rights Reserved.