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The Journal of Neuroscience, July 23, 2008, 28(30):7563-7573; doi:10.1523/JNEUROSCI.1659-08.2008

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Development/Plasticity/Repair
Analysis of Peripheral Nerve Expression Profiles Identifies a Novel Myelin Glycoprotein, MP11

Elizabeth J. Ryu,^1 * Mao Yang,^1 * Jason A. Gustin,¹ Li-Wei Chang,¹ Robert R. Freimuth,³ Rakesh Nagarajan,¹ and Jeffrey Milbrandt^1,2

Departments of ¹Pathology and Immunology, ²HOPE Center for Neurological Disorders, Washington University School of Medicine, St. Louis, Missouri 63110, and ³Division of Biomedical Informatics, Mayo Clinic College of Medicine, Rochester, Minnesota 55905

Correspondence should be addressed to Dr. Jeffrey Milbrandt, Department of Pathology and Immunology, HOPE Center for Neurological Disorders, Washington University School of Medicine, 660 South Euclid Avenue, Box 8118, St. Louis, MO 63110. Email: jmilbrandt{at}wustl.edu

The myelin sheath insulates axons and allows for rapid salutatory conduction in the nervous system of all vertebrates. The formation of peripheral myelin requires expression of the transcription factor Egr2, which is responsible for inducing such essential myelin-associated genes as Mpz, Mbp, Pmp22, and Mag. Using microarray analysis to compare gene expression patterns in peripheral nerve during development, during remyelination after nerve injury, and in a congenital hypomyelinating mouse model, we identified an evolutionarily conserved novel component of myelin called Mp11 (myelin protein of 11 kDa). The Mp11 genomic locus contains multiple conserved Egr binding sites, and Mp11 induction is regulated by the expression of Egr2. Similar to other Egr2-dependent genes, it is induced during developmental myelination and remyelination after nerve injury. Mp11 is a glycoprotein expressed preferentially in the myelin of the peripheral nervous system versus CNS and is specifically localized to the Schmidt-Lanterman incisures and paranodes of peripheral nerve. The Mp11 protein contains no identifiable similarity to other known protein domains or motifs. However, like other myelin genes, strict Mp11 expression levels are a requirement for the in vitro myelination of DRG neurons, indicating that this previously uncharacterized gene product is a critical component of peripheral nervous system myelin.

Key words: Mp11; Egr2; myelination; Schmidt-Lanterman incisures; paranode; expression profiling

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Received April 16, 2008; revised May 23, 2008; accepted May 28, 2008.

Correspondence should be addressed to Dr. Jeffrey Milbrandt, Department of Pathology and Immunology, HOPE Center for Neurological Disorders, Washington University School of Medicine, 660 South Euclid Avenue, Box 8118, St. Louis, MO 63110. Email: jmilbrandt{at}wustl.edu

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