In the February 1st issue of Genes & Development, Dr. Brian Popko (The University of Chicago) and colleagues describe how mutation of a gene called ZFP191 leads to disordered CNS myelination in mice — reminiscent of what is seen in human multiple sclerosis (MS) patients.
The paper will be released online ahead of print at www.genesdev.org.
MS is a chronic autoimmune disorder, in which the body attacks and destroys the myelin sheath that insulates and protects nerve fibers of the central nervous system (the brain, spinal cord and optic nerves). Demyelination disrupts the conduction of electrical impulses along nerve fibers, and results in regional neural deficits. MS symptoms range from tingling and numbness in limbs, to loss of vision and paralysis.
It is estimated that MS affects 400,000 people in the US and approximately 2.5 million worldwide.
Dr. Popko and colleagues identified a gene called 
ZFP191 as being necessary for the development of oligodendrocyte cells, which – in their fully mature form – produce myelin. The researchers found that mice harboring a single mutation in ZFP191 display tremors and seizures, caused by a severe deficiency in CNS myelination.
ZFP191 appears to be the first factor identified to be critical for the myelinating function of oligodendrocytes.
The failure of Zfp191-mutant mouse oligodendrocytes to successfully myelinate their targets is reminiscent of human MS lesions, where re-myelination of damaged tracts fails to occur efficiently even when apparently mature oligodendrocytes are present in the area.
While further research to delineate the precise targets of ZFP191 is needed, this work holds promising clinical value as a potential therapeutic pathway to promote re-myelination, reduce the accumulation of MS lesions and slow disease progression.
Full Paper:
ZFP191 is required by oligodendrocytes for CNS myelination by Shen Yi B Howng, Robin L Avila, Ben Emery, Maria Traka, Wenshehng Lin, Trent Watkins, Susan Cook, Roderick Bronson, Muriel Davisson, Ben A Barres, and Brian Popko
Related Article:
A Shaky Mouse & the Brain’s Power Cables
Mouse Study May Advance Multiple Sclerosis Research – BusinessWeek
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A supporter of ours on Facebook asked whether this mouse model was very different from the traditional EAE Mouse model — whether it was closer to human MS.
Professor Brian Popko, generously took the time to write back a response:
This mouse and the EAE model are very different.
EAE is an acquired disorder, secondary to an immunization, in which the animal develops an immune-response against its own myelin. EAE is an adult-onset demyelinating disorder.
The Zfp191 mutant mouse is the result of a genetic abnormality that results in a developmental myelination defect. These animals never develop a normal myelin sheath.
Nevertheless, the Zfp191 mutant has value in the study of MS because the genetic defect results in the block of the myelination process at a point that appears very similar to that which occurs in MS patients that fail to remyelinate their demyelinated axons.
Comment by Justine Lam — January 19, 2010 @ 12:25 pm
I am new to this blog and I am certain that this question has been asked before, but, can this myelin repair study be appled to patients that have Transverse Myelitis?
Comment by Jessica — February 2, 2010 @ 6:26 pm
Jessica,
Thanks for posting your question. We receive this question often by email about whether our work will benefit other demyelinating disease research.
The research efforts of the Myelin Repair Foundation are focused solely on restoring myelin in people with multiple sclerosis, since it is the probably the most common demyelinating disease to affect the central nervous system (CNS).
We do expect the discoveries made by our research team will have spill over benefits to other demyelinating diseases and neurobiology in general, both in the CNS and in the peripheral nervous system. But we can’t make any promises in that area.
Justine
Comment by Justine Lam — February 4, 2010 @ 11:00 am