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Oligodendrocytes expressing exclusively the DM20 isoform of the proteolipid protein gene: Myelination and development
Author(s) -
Spörkel Olaf,
Uschkureit Thomas,
Büssow Heinrich,
Stoffel Wilhelm
Publication year - 2002
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.10014
Subject(s) - proteolipid protein 1 , myelin , biology , oligodendrocyte , myelin proteolipid protein , gene isoform , microbiology and biotechnology , citrullination , myelin basic protein , biochemistry , central nervous system , gene , amino acid , neuroscience , arginine , citrulline
Abstract Oligodendroglia and Schwann cells synthesize myelin‐specific proteins and lipids for the assembly of the highly organized myelin membrane of the motor‐sensory axons in the central (CNS) and peripheral nervous system (PNS), respectively, allowing rapid saltatory conduction. The isoforms of the main myelin proteins, the peripheral myelin basic isoproteins (MBP) and the integral proteolipid proteins, PLP and DM20, arise from alternative splicing. Activation of a cryptic splice site in exon III of plp leads to the deletion of 105 bp encoding the PLP‐specific 35 amino acid residues within the cytosolic loop 3 of the four‐transmembrane domain (TMD) integral membrane protein. To study the different proposed functions of DM20 during the development of oligodendrocytes and in myelination, we targeted the plp locus in embryonic stem cells by homologous recombination by a construct, which allows solely the expression of the DM20 specific exon III sequence. The resulting dm20 only mouse line expresses exclusively DM20 isoprotein, which is functionally assembled into the membrane, forming a highly ordered and tightly compacted myelin sheath. The truncated cytosolic loop devoid of the PLP‐specific 35 amino acid residues, including two thioester groups, had no impact on the periodicity of CNS myelin. In contrast to the PLP/DM20‐deficient mouse, mutant CNS of dm20 only mice showed no axonal swellings and neurodegeneration but a slow punctuated disintegration of the compact layers of the myelin sheath and a rare oligodendrocyte death developing with aging. GLIA 37:19–30, 2002. © 2002 Wiley‐Liss, Inc.