Identification of a New Exon in the Myelin Proteolipid Protein Gene Encoding Novel Protein Isoforms That Are Restricted to the Somata of Oligodendrocytes and Neurons

Overview

Journal J Neurosci

Specialty Neurology

Date 1999 Sep 24

PMID 10493736

Citations 29

Authors

E R Bongarzone

C W Campagnoni

K Kampf

E C JACOBS

V W Handley

V Schonmann

A T Campagnoni

Affiliations

Soon will be listed here.

Abstract

The myelin proteolipid protein (PLP) gene (i.e., the PLP/DM20 gene) has been of some interest because of its role in certain human demyelinating diseases, such as Pelizaeus-Merzbacher disease. A substantial amount of evidence, including neuronal pathology in knock-out and transgenic animals, suggests the gene also has functions unrelated to myelin structure, but the products of the gene responsible for these putative functions have not yet been identified. Here we report the identification of a new exon of the PLP/DM20 gene and at least two new products of the gene that contain this exon. The new exon, located between exons 1 and 2, is spliced into PLP and DM20 mRNAs creating a new translation initiation site that generates PLP and DM20 proteins with a 12 amino acid leader sequence. This leader sequence appears to target these proteins to a different cellular compartment within the cell bodies of oligodendrocytes and away from the myelin membranes. Furthermore, these new products are also expressed in a number of neuronal populations within the postnatal mouse brain, including the cerebellum, hippocampus, and olfactory system. We term these products somal-restricted PLP and DM20 proteins to distinguish them from the classic PLP and DM20 proteolipids. They represent putative candidates for some of the nonmyelin-related functions of the PLP/DM20 gene.

Citing Articles

in the enteric nervous system is preferentially expressed during early postnatal development in mouse as DM20, whose expression appears reliant on an intronic enhancer.

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transgenic mice reveal that splice variants containing "human-specific" exons are relatively minor in comparison to the archetypal transcript and that an upstream regulatory element bolsters expression during early postnatal brain development.

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The wmN1 Enhancer Region of the Mouse Myelin Proteolipid Protein Gene (mPlp1) is Indispensable for Expression of an mPlp1-lacZ Transgene in Both the CNS and PNS.

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The wmN1 enhancer region in intron 1 is required for expression of human PLP1.

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