Alternative titles; symbols
HGNC Approved Gene Symbol: OMG
Cytogenetic location: 17q11.2 Genomic coordinates (GRCh38) : 17:31,294,647-31,297,239 (from NCBI)
In the course of efforts to identify the gene mutated in neurofibromatosis type I (NF1; 162200), Viskochil et al. (1991) found 3 genes embedded within an intron of the NF1 gene (613113). The cDNA sequence of one of these genes encodes oligodendrocyte-myelin glycoprotein (OMG).
Viskochil et al. (1991) reported that the OMG gene spans at least 2.7 kb of genomic DNA and maps within 4 kb of the breakpoint of a balanced chromosomal translocation carried by an individual with NF1. OMG is similar in genomic structure to 2 other expressed genes, EVI2A (158380) and EVI2B (158381), which lie approximately 20 and 5 kb telomeric to the OMG locus, respectively. All 3 genes have the same transcriptional orientation and are contained within 1 intron of NF1, which is transcribed from the opposite strand. Whether altered expression of OMG plays a role in the clinical heterogeneity of NF1 remained to be determined.
Mikol et al. (1990) found a single intron in the 5-prime untranslated region of the OMG gene; the coding region was uninterrupted by an intron. The placement of the single intron in the OMG gene is identical to that in the gene for the alpha-chain of platelet glycoprotein Ib (231200), which, along with OMG, belongs to a family of proteins sharing 2 distinct structural domains: an NH2-terminal cysteine-rich domain and an adjacent domain of tandem leucine-rich repeats. No obvious promoter elements were noted in the 5-prime and 3-prime flanking regions.
By hybridization of a genomic clone to metaphase cells, Mikol et al. (1990) localized the OMG gene to 17q11-q12, the region to which the NF1 gene had previously been mapped. Mikol et al. (1993) showed that in the mouse the OMGP gene has a single intron in the 5-prime untranslated region in exactly the same position as the sole intron in the gene for the human protein. The conservation of the nucleotide sequences of the coding, noncoding, and flanking regions of the 2 genes was remarkable. No mapping information in the mouse was provided.
Habib et al. (1998) reported that OMG, like neurofibromin (see NF1), has growth suppressive effects and downregulates mitogenic signaling pathways closely related to those influenced by neurofibromin. Overexpression of OMG altered mitogenic signaling in fibroblasts. Cells overexpressing OMG grew more slowly in serum compared to controls and showed a partial G1 block upon cell cycle analysis. PDGF (e.g., 190040) is the primary mitogen for fibroblasts in serum. Overexpression of OMG altered PDGF signaling in fibroblasts, which resulted in a block of mitogenic signaling. PDGF-induced activation of c-src (190090) was blocked, as was the induction of c-myc (190080) and c-fos (164810), while tyrosine phosphorylation of the PDGF-beta receptor (173410) and PLC-gamma-1, and induction of c-jun (165160), were intact. Habib et al. (1998) demonstrated that structurally unrelated products of 2 genes, 1 of which is embedded within the other, may exercise closely related functions. Their data also raised the possibility of a role for OMG in disorders of cell proliferation, such as NF1.
Wang et al. (2002) demonstrated that a glycosylphosphatidylinositol (GPI)-anchored central nervous system (CNS) myelin protein, oligodendrocyte-myelin glycoprotein (OMGP), is a potent inhibitor of neurite outgrowth in cultured neurons. Like NOGOA (604475), OMGP contributes significantly to the inhibitory activity associated with CNS myelin. To further elucidate the mechanisms that mediate this inhibitory activity, Wang et al. (2002) screened an expression library and identified the NOGO receptor (NGR; 605566) as a high affinity OMGP-binding protein. Cleavage of NOGO receptor and other GPI-linked proteins from the cell surface renders axons of dorsal root ganglia insensitive to OMGP. Introduction of exogenous NOGO receptor confers OMGP responsiveness to otherwise insensitive neurons. Thus, OMGP is an important inhibitor of neurite outgrowth that acts through the NOGO receptor and its associated receptor complex. Wang et al. (2002) suggested that interfering with the OMGP/NOGO receptor pathway may allow lesioned axons to regenerate after injury in vivo.
Huang et al. (2005) showed that nodal membranes isolated from the CNS of mammals restricted neurite outgrowth of cultured neurons. Proteomic analysis of these membranes revealed several inhibitors of neurite outgrowth, including OMGP. In rat spinal cord, Omgp was not localized to compact myelin, as previously thought, but to oligodendroglia-like cells, whose processes converge to form a ring that completely encircles the nodes. In Omgp-null mice, CNS nodes were abnormally wide and collateral sprouting was observed. Huang et al. (2005) concluded that nodal ensheathment in the CNS may stabilize the node and prevent axonal sprouting.
With the use of expression cloning, Atwal et al. (2008) found that paired immunoglobulin-like receptor B (PIRB; 604820), which has been implicated in nervous system plasticity, is a high-affinity receptor for NOGO, MAG (159460), and OMGP. Interfering with PIRB activity, either with antibodies or genetically, partially rescued neurite inhibition by NOGO66, MAG, OMGP, and myelin in cultured neurons. Blocking both PIRB and NGR activities led to near-complete release from myelin inhibition. Atwal et al. (2008) concluded that their results implicated PIRB in mediating regeneration block, identified PIRB as a potential target for axon regeneration therapies, and provided an explanation for the similar enhancements of visual system plasticity in PIRB and NGR knockout mice.
Atwal, J. K., Pinkston-Gosse, J., Syken, J., Stawicki, S., Wu, J., Shatz, C., Tessier-Lavigne, M. PirB is a functional receptor for myelin inhibitors of axonal regeneration. Science 322: 967-970, 2008. [PubMed: 18988857] [Full Text: https://doi.org/10.1126/science.1161151]
Habib, A. A., Gulcher, J. R., Hognason, T., Zheng, L., Stefansson, K. The OMgp gene, a second growth suppressor within the NF1 gene. Oncogene 16: 1525-1531, 1998. [PubMed: 9569019] [Full Text: https://doi.org/10.1038/sj.onc.1201683]
Huang, J. K., Phillips, G. R., Roth, A. D., Pedraza, L., Shan, W., Belkaid, W., Mi, S., Fex-Svenningsen, A., Florens, L., Yates, J. R., III, Colman, D. R. Glial membranes at the node of Ranvier prevent neurite outgrowth. Science 310: 1813-1817, 2005. [PubMed: 16293723] [Full Text: https://doi.org/10.1126/science.1118313]
Mikol, D. D., Alexakos, M. J., Bayley, C. A., Lemons, R. S., Le Beau, M. M., Stefansson, K. Structure and chromosomal localization of the gene for the oligodendrocyte-myelin glycoprotein. J. Cell Biol. 111: 2673-2679, 1990. [PubMed: 2277079] [Full Text: https://doi.org/10.1083/jcb.111.6.2673]
Mikol, D. D., Rongnoparut, P., Allwardt, B. A., Marton, L. S., Stefansson, K. The oligodendrocyte-myelin glycoprotein of mouse: primary structure and gene structure. Genomics 17: 604-610, 1993. [PubMed: 8244377] [Full Text: https://doi.org/10.1006/geno.1993.1379]
Viskochil, D., Cawthon, R., O'Connell, P., Xu, G. F., Stevens, J., Culver, M., Carey, J., White, R. The gene encoding the oligodendrocyte-myelin glycoprotein is embedded within the neurofibromatosis type 1 gene. Molec. Cell. Biol. 11: 906-912, 1991. [PubMed: 1899288] [Full Text: https://doi.org/10.1128/mcb.11.2.906-912.1991]
Wang, K. C., Koprivica, V., Kim, J. A., Sivasankaran, R., Guo, Y., Neve, R. L., He, Z. Oligodendrocyte-myelin glycoprotein in a Nogo receptor ligand that inhibits neurite outgrowth. Nature 417: 941-944, 2002. [PubMed: 12068310] [Full Text: https://doi.org/10.1038/nature00867]