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The research team was led by
Stuart A. Lipton,
M.D., Ph.D., a clinical neurologist and Professor and Director of the
Del E. Webb
Neuroscience, Aging and Stem Cell Research Center at Burnham.
“These results give us a good hint of how to look at Rett Syndrome and
potentially other forms of autism in humans,” said Dr. Lipton. “Having
identified a mutation that causes
this defect, we can track what happens. Perhaps we can correct it in a mouse,
and if so, eventually correct it in humans.”
Discovered in Dr. Lipton’s laboratory, MEF2C turns on specific genes which drive
stem cells to become nerve cells. When MEF2C was deleted from neural stem cells
in mice, there was a faulty distribution of neurons accompanied by severe
developmental problems. Adult mice lacking MEF2C in their brains displayed
abnormal anxiety-like behaviors, decreased cognitive function and marked paw
clasping, a behavior which may be analogous to hand wringing, a notable feature
in humans with Rett syndrome.
“There’s a yin and yang to this MEF2C protein,” said Dr. Lipton. “My laboratory
recently showed that MEF2C induces embryonic stem cells to become neurons. In
this new research, we show that knocking out MEFC2 in the brain results in mice
with smaller brains, fewer neurons and reduced neuronal activity. The
commonality is the protein’s association in making new neurons.”
Collaborators were Drs. Hao Li, Shu-ichi Okamoto, Nobuki Nakanishi and Scott
McKercher, of Burnham, as well as Dr. Amanda Roberts from The Scripps Research
Institute and Dr. John Schwarz from the Albany Medical Center.
Rett syndrome, a form of autism, afflicts more girls than boys and results in
poor brain development, repetitive hand motions, altered anxiety behaviors and
the inability to speak. Patients with Rett Syndrome also suffer from seizures
and other debilitating neurological symptoms.
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