Structure and chromosomal localization of the gene for the oligodendrocyte-myelin glycoprotein.

Abstract

Abstract. Utilizing a eDNA clone encoding the oligodendrocyte-myelin glycoprotein (OMgp) to screen a human genomic DNA library, we have obtained a clone that contains the OMgp gene. The genornic clone was restriction mapped and the OMgp gene and its 5' and 3' flanking regions were sequenced. A single intron is found in the 5' untranslated region of the gene, while the coding region is uninterrupted by an intron. This placement of a single intron in the OMgp gene is identical to that of the gene for the o~-chain of platelet glycoprotein Ib, which, along with OMgp, belongs to a family of proteins sharing two distinct structural domains: an NH2-terminal cysteine-rich domain and an adjacent domain of tandem leucine-rich repeats. Hence, it is possible that this family of proteins is not only related in terms of primary structure, but also through similar gene structure. Sequence comparison of the 5' and 3' flanking regions did not reveal striking similarities to other DNA sequences, and no obvious promoter elements were noted. By hybridization of the genomic clone to metaphase cells, we have localized the human OMgp gene to chromosome 17 bands qll-12, a region to which the neurofibromatosis type 1 gene has been previously mapped.T HE oligodendrocyte-myelin glycoprotein (OMgp) ~ is a highly glycosylated protein of oligodendrocytes and central nervous system myelin which appears to be localized at the paranodal region of the myelin sheath (Mikol and Stefansson, 1988). OMgp is anchored in the plasma membrane as a 120-kD glycoslyphosphatidylinositol-linked form that can be released from the membrane upon incubation with phospholipase C to generate a soluble 105-kD polypeptide. Based on eDNA sequence, the predicted primary structure of OMgp consists of four domains (Mikol et al., 1990). At the NH2-terminus there is a 32-amino acid cysteine-rich (CR) motif. This is followed by a domain consisting of 7 I/2 tandem leucine-rich repeats (LRs) of 24 amino acids each, and a domain of 4 1/2 repeats of 40 residues each that are rich in serines and threonines. A hydrophobic COOH-terminal segment is most likely cleaved concomitant with the attachment of a phosphatidylinositolcontaining glycan (Cross, 1990).

Oligodendrocyte‐myelin glycoprotein (OMgp) is an inhibitor of neurite outgrowth

“…Authentic samples of OMgp purified from mouse or human brain by a different procedure evinced the same inhibitory properties as arretin. This glycoprotein of 110–120 kDa (440 amino acids) is glycosylphosphatidylinositol‐linked to the cell membrane in myelinating oligodendrocytes, and is localized to the glial–axonal interface of myelinated axons (Mikol et al . 1990a,b, 1993; Habib et al .…”

Expression of the Oligodendrocyte‐Myelin Glycoprotein by Neurons in the Mouse Central Nervous System

“…The human OMgp gene is interrupted by a single intron, which is found in the 5' untranslated region (Mikol et al, 1990b). Originally the gene was mapped to human chromosome 17 bands qi 1-12, the region to which the neurofibromatosis type I (NP1) gene had also been mapped.…”

Report of the committee on the genetic constitution of chromosome 17

“…Most of these were also included in the Chromosome 17 Workshop report (Table 2 in (Fain et al, 1991)). (Mikol et al, 1990) 17q21 PBH prohibitin (White et al, 1991b) 17q23.1-q25.3 SCN4A sodium channel, type IV, alpha polypeptide (Ptacek et al, 1991c) (George et al, 1991) (Fontaine et al, 1990) (Ptacek et al, 1991a) (Ptacek et al, 1991b) pter D17S34 D17S5 (TP53, D17S31, POLR2) D17S1 MYH2 D17S121 (CMT1A, D17S122) D17S71 D17S29 D17S58 D17Z1 CRYB1 (NF1, OMG, EVI2B, EVI2A) (D17S57, D17S73) D17S37 D17S36 D17S108 PPY (H0X2,C17M1) NGFR D17S41 D17S74 GH1 D17S40 D17S42 D17S4 D17S26 D17S75 (D17S24, D17S27 CD7 D17S254 EN03 P4HB COL1A1 D17S258 EPB3 PENT CRYB1 D17S261 ERBA2L PFN1 CSF3 D17S377 ERBB2 PPY D17S5 D17S379 EVI2A RARA D17S29 D17S445 FDXR TCF2 D17S33 D17S513 GAA THRA1 D17S71 D17S514 GAS TK1 D17S122 D17S515 GIP TP53 D17S124 D17S516 GLUT4 UBB D17S126 D17S518 GP2B D17S128 D17S520 MPO D17S145 D17Z1 NF1…”