|Researchers Discover Gene Crucial for Nerve
Researchers funded by the National Institutes of Health have discovered
how a defect in a single master gene disrupts the process by which
several genes interact to create myelin, a fatty coating that covers
nerve cells and increases the speed and reliability of their electrical
The discovery has implications for understanding disorders of
myelin production. These disorders can affect the peripheral nervous
system — the nerves outside the brain and spine. These disorders
are known collectively as peripheral neuropathies. Peripheral neuropathies
can result in numbness, weakness, pain, and impaired movement.
They include one of the most common genetically inherited disorders,
Charcot-Marie-Tooth disease, which causes progressive muscle weakening
The myelin sheath that surrounds a nerve cell is analogous to
the insulating material that coats an electrical cord or wire,
keeping nerve impulses from dissipating, allowing them to travel
farther and faster along the length of the nerve cell.
The researchers discovered how a defect in just one copy of the
gene, known as early growth response gene 2 (EGR2) affects the
normal copy of the gene as well as the functioning of other genes,
resulting in peripheral neuropathy.
“The researchers have deciphered a key sequence essential to the
assembly of myelin,” said Duane Alexander, M.D., Director of the
NICHD, the NIH institute that funded the study. “Their discovery
will provide important insight into the origins of disorders affecting
The study appears in the online version of Molecular and Cellular
John Svaren, Ph.D., an associate professor in the Department of
Comparative Bioscience at the University of Wisconsin — Madison’s
School of Veterinary Medicine, worked with colleagues Scott E.
LeBlanc, and Rebecca M. Ward, to conduct the study. Dr. Svaren
is an affiliate of NICHD-funded mental retardation and developmental
disabilities research center at the Waisman Center at the University
Until this discovery, researchers did not fully understand the
complex genetic process that enables Schwann cells, found in the
peripheral nervous system, to coat nerves with myelin.
The Newly Discovered Role of EGR2
During this study, the scientists found that EGR2 produces a protein
that activates several other genes necessary for myelin production.
Some of these genes contain the information needed to make peripheral
myelin protein-22 (PMP-22) and myelin protein zero (MPZ). MPZ is
the most abundant protein in myelin in the peripheral nervous system.
The overproduction or underproduction of the proteins PMP22 and
MPZ account for the majority of inherited peripheral neuropathies,
Dr. Svaren said.
Ultimately, the sequence of activating genes “switches on” the
Schwann cell, which wraps the nerve axon, the arm-like projection
that conveys nerve impulses, in a myelin sheath.
The scientists’ research also resolved a long-standing mystery
surrounding why a single mutant copy of the EGR2 gene disrupts
the functioning of the normal EGR2 gene, leading to a disorder
of the nervous system.
In many genetic conditions, the unaffected copy of an affected
gene continues to produce its protein. However, the researchers
found that the mutant EGR2 copy interferes with the interaction
between the normal EGR2 gene and another myelin gene, SOX10, as
the two try to work together to produce the myelin protein MPZ.
By understanding the process which creates myelin, researchers
may now be able to investigate new therapies for disorders affecting
“Our research has uncovered a whole new mechanism for regulating
myelin genes,” said Dr. Svaren. “Our hope is to exploit this knowledge
so that we can adjust the levels of myelin genes such as PMP22
and MPZ, and thereby create an effective treatment for myelin diseases.”
Understanding the process by which nerve cells are myelinated
also could be applied to other disorders as well, Dr. Svaren said.
Diabetic neuropathy, which results in a loss of feeling in the
extremities, also is thought to involve myelin production.
Dr. Svaren added that it is possible that the current study’s
findings about myelin production in the peripheral nervous system
could lead to greater understanding of how myelination takes place
in the central nervous system (the brain and spinal cord). Myelination
in the central nervous system is not well understood. Multiple
sclerosis, a degenerative muscular disorder that can be fatal,
results from the destruction of myelin in the central nervous system.
Information about peripheral neuropathies is available from the
National Library of Medicine, at: http://www.nlm.nih.gov/medlineplus/ency/article/000593.htm and http://www.nlm.nih.gov/medlineplus/ency/article/000727.htm.
Information about Charcot-Marie-Tooth syndrome and multiple sclerosis
is available from The National Institute of Neurological Disorders
and Stroke at: http://www.ninds.nih.gov/disorders/charcot_marie_tooth/charcot_marie_tooth.htm and http://www.ninds.nih.gov/disorders/multiple_sclerosis/multiple_sclerosis.htm.
The NICHD sponsors research on development, before and after birth;
maternal, child, and family health; reproductive biology and population
issues; and medical rehabilitation. For more information, visit
the Institute’s website at http://www.nichd.nih.gov.
The National Institutes of Health (NIH) — The Nation's
Medical Research Agency — includes 27 Institutes and
Centers and is a component of the U.S. Department of Health and
Human Services. It is the primary federal agency for conducting
and supporting basic, clinical and translational medical research,
and it investigates the causes, treatments, and cures for both
common and rare diseases. For more information about NIH and
its programs, visit www.nih.gov.