ISOLATION AND CHARACTERIZATION OF A NOVEL OLIGODENDROCYTE-SPECIFIC PROTEIN

Myelin plays a critical role in nervous system function and alteration s in myelin-specific proteins cause a variety of neurologic disorders. We isolated a novel cDNA from the CNS that shares little nucleotide s equence homology with previously reported genes but appears to encode a protein related to peripheral myelin protein-22 (PMP-22) based on it s amino acid sequence, predicted structure, and cellular localization. PMP-22 is important in peripheral myelination and Schwann cell prolif eration, and mutations in its gene cause diseases of peripheral nerves . The isolated cDNA is 1.8 kb in length with an open reading frame of 621 bp. Northern blot analysis detected hybridization of labeled cDNA with a single 2.1-kb transcript only in the CNS. In situ hybridization revealed expression of this cDNA in oligodendrocytes of brain and spi nal cord as well as in oligodendrocyte-enriched cultures; therefore we have named it oligodendrocyte-specific protein (OSP) cDNA. An OSP-spe cific polyclonal antibody reacted with a single 22-kd protein present in CNS myelin and oligodendrocytes. Developmental expression of OSP mR NA in the spinal cord was similar to that of the mRNA for a major myel in protein, proteolipid protein (PLP), and similar to PMP-22 in periph eral nerves. Since OSP is localized to oligodendrocytes and myelin, ha s a similar structure with PMP-22, and has a developmental pattern of expression like other myelin proteins, it probably has an important ro le in CNS myelinogenesis.