Disease relevance of OMG

• The gene encoding the oligodendrocyte-myelin glycoprotein is embedded within the neurofibromatosis type 1 gene [1].
• The possible three-dimensional structure of the LRR domain of OMgp was modelled using the structure of Yersinia pestis YopM cytotoxin as a template [2].
• The oligodendrocyte myelin glycoprotein (OMgp) inhibits neurite outgrowth and axonal regeneration after brain injury, but its normal function remains unknown [2].
• More than half of patients presenting with symptoms isolated to these muscles (OMG) develop generalized myasthenia gravis (GMG) over the course of their illness [3].
• Further, the conjugates of OM (OMG) accumulated in patients with acute renal failure could contribute to the sedation [4].

Psychiatry related information on OMG

• Mutations and novel polymorphisms in coding regions and UTRs of CDK5R1 and OMG genes in patients with non-syndromic mental retardation [5].
• Molecular analysis of the oligodendrocyte myelin glycoprotein gene in autistic disorder [6].

High impact information on OMG

• The complete primary structure of the human oligodendrocyte-myelin glycoprotein (OMgp), a glycophospholipid-linked membrane protein of oligodendrocytes and central nervous system myelin, has been determined [7].
• By hybridization of the genomic clone to metaphase cells, we have localized the human OMgp gene to chromosome 17 bands q11-12, a region to which the neurofibromatosis type 1 gene has been previously mapped [8].
• OMgp shares the first three of its four domains with the platelet glycoprotein Ib, which is responsible for the initial adhesion of platelets to the exposed subendothelium during hemostasis [7].
• This placement of a single intron in the OMgp gene is identical to that of the gene for the alpha-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 [8].
• In addition, we report that a subpopulation of OMgp molecules contains the HNK-1 carbohydrate, which has been shown to mediate interactions among cells in the central nervous system [7].

Biological context of OMG

• OMGP spans at least 2.7 kb of genomic DNA, and it maps within 4 kb of the breakpoint of a balanced chromosomal translocation carried by an individual with NF1 [1].
• The genomic clone was restriction mapped and the OMgp gene and its 5' and 3' flanking regions were sequenced [8].
• Utilizing a cDNA clone encoding the oligodendrocyte-myelin glycoprotein (OMgp) to screen a human genomic DNA library, we have obtained a clone that contains the OMgp gene [8].
• OMgp leucine-rich repeat domain is also implicated in the inhibition of cell proliferation [9].
• The predicted arrangement of the LRR segments is compatible with a function of OMgp as a binding protein [2].

Anatomical context of OMG

• OMG encodes for an inhibitor of neurite outgrowth by the binding to the Nogo-66 receptor (RTN4R) [5].
• Based on its developmental expression, localization and structure, OMgp may also be involved in the formation and maintenance of myelin sheaths [9].
• The oligodendrocyte myelin glycoprotein (OMgp) is a glycosylphosphatidylinositol-anchored protein expressed by neurons and oligodendrocytes in the central nervous system (CNS) [9].
• The Lingo-1-NgR-p75NTR complex is shown to confer the inhibitory effects on nerve cell regeneration of Nogo-66, OMgP, and MAG by activating the small guanosine triphosphatase (GTPase) RhoA [10].
• OMG sera, furthermore, detected a protein of about 45 kDa in the pellet fraction of eye muscle but failed to do so after adsorption with skeletal muscle fractions [11].

Associations of OMG with chemical compounds

• Together with glycoprotein Ib and several other proteins, OMgp belongs to a family of proteins that contain both an NH2-terminal cysteine-rich motif and an adjacent series of LRs [7].
• The relative contribution of Nogo, myelin-associated glycoprotein, chondroitin sulfate proteoglycan and oligodendrocyte myelin glycoprotein to myelin inhibition can be assessed [12].
• CONCLUSIONS: Uridine and OMG each have antidepressant-like effects in rats [13].
• MDASS uses GEOGINE (GEOmetrical enGINE), a state-of-the-art OMG (Ontological Model Generator) based on n-D Tensor Moment Invariants for shape/texture effective description [14].
• In summary, OMG has a good prognosis in most patients, with corticosteroids and azathioprine being the major treatment options [15].

Other interactions of OMG

• Whether altered expression of OMGP might play a role in the clinical heterogeneity of NF1 is as yet unclear [1].
• Prediction of mRNA and protein secondary structures revealed that two changes lead to putative structural alterations in the mutated c.2254C>G CDK5R1 3'UTR and in OMG T408A gene product [5].
• The RTN4R gene is located in the 22q11 region and it encodes a subunit of the receptor complex (RTN4R-p75NTR) which results in neuronal growth inhibitory signals in response to Nogo-66, MAG or OMG signaling [16].
• NgR binds to several myelin-associated ligands (Nogo-66, myelin associated glycoprotein, and oligodendrocyte-myelin glycoprotein), which, among other inhibitory proteins, impair axonal regeneration in the CNS of adult mammals [17].
• In the absence of thymoma, thymectomy is usually not considered in OMG, although a few studies have described histological abnormalities in thymuses from patients with OMG [15].

Analytical, diagnostic and therapeutic context of OMG

• We have therefore assessed the ability of single-fiber electromyography (SFEMG) to predict the development of GMG in patients presenting with OMG [3].
• Blood samples were assayed by HPLC and by FPIA and analysis was performed before and after hydrolysis of OMG [4].
• Microarray analysis revealed the expression of MAG, MOBP and OMG genes in HOG cells [18].
• Since prospective treatment trials have not been performed, basic management strategies for OMG have to be deduced from retrospective studies, trials in GMG, and generally accepted clinical experience [15].
• By immunocytochemistry, OMgp was localized to the paranodal region of myelin, and the protein homologous to the hyaluronate binding domain of versican was localized to the nodal gap in peripheral nerve [19].

References