Disease relevance of GPNMB

• As the gene coding for human GPNMB was localized to chromosome 7p15, a locus involved in the human inherited disease cystoid macular edema, also known as dominant cystoid macular dystrophy (OMIM 153880) we highly suggest that GPNMB is a candidate gene for this human inherited disease [1].
• A fully human monoclonal antibody, designated CR011, was generated to the extracellular domain of GPNMB and characterized for growth-inhibitory activity against melanoma [2].
• EXPERIMENTAL DESIGN: We have done genetic and immunohistochemical evaluation of human GBM to determine incidence, distribution, and pattern of localization of GPNMB antigens in brain tumors as well as survival analyses [3].
• We have shown that HNK-1 recognizes the human neuroblastoma lines SMS-KCNR, SMS-KAN, NMB/N7, and IMR/5 [4].
• Phase-variation of the truncated lipo-oligosaccharide of Neisseria meningitidis NMB phosphoglucomutase isogenic mutant NMB-R6 [5].

High impact information on GPNMB

• Transcript abundance of the cathepsins, novel genes, pulmonary and activation-regulated chemokine (PARC), and NMB, a putative tumor suppressor gene, was greatly increased [6].
• However, when linked to the cytotoxic agent monomethylauristatin E (MMAE) to generate the CR011-vcMMAE antibody-drug conjugate, this reagent now potently and specifically inhibited the growth of GPNMB-positive melanoma cells in vitro [2].
• Ectopic overexpression and small interfering RNA transfection studies showed that GPNMB expression is both necessary and sufficient for sensitivity to low concentrations of CR011-vcMMAE [2].
• Consistently, PxB neutralized inflammatory responses elicited by the lptA mutant lipooligosaccharide more efficiently than those induced by wild-type lipooligosaccharide. mariner mutants with increased resistance to PxB were also identified in NMB background and found to contain insertions within the pilMNOPQ operon involved in pilin biogenesis [7].
• Three cell lines (IMR-32, NMB and Kelly) were investigated and found to bind tritiated beta h-EP with an apparent dissociation constant of 2.2-4.2 nM [8].

Biological context of GPNMB

• GPNMB is a highly glycosylated type I transmembrane protein that shares significant sequence homology to several melanosomal proteins [1].
• To address the potential functions of GPNMB we analysed its mRNA-expression during murine embryonic development [1].
• These dichotomous roles suggest that HGFIN could be linked to cell cycle regulation [9].
• This study cloned and analyzed two fragments in the 5' flanking region of HGFIN: HGFIN-RM/2.0: 2.0 kb upstream of Exon 1; HGFIN-RM/1.5: 5' deletion (500 bp) of HGFIN-RM/2 [9].
• Reporter gene activities with HGFIN-RM/2.0 and HGFIN-RM/1.5 in cells with different p53 levels showed that p53 is relevant to HGFIN activities [9].

Anatomical context of GPNMB

• In both non-pigmented cell lines, the EGFP-GPNMB fusion protein was localized to vesicular, endosomal like structures [1].
• The murine homologue of the human glycoprotein (transmembrane) NMB (GPNMB) gene was identified by subtractive cloning from in vitro cultured murine primary osteoblast cells and subsequent RACE-PCR [1].
• Sequence homology to known melanosomal proteins, mRNA expression and subcellular localization are suggestive for GPNMB as an intracellular, endosomal/melanosomal compartment specific protein important for melanin biosynthesis and the development of the retinal pigment epithelium and iris [1].
• A comparative study of circulating human reticulocytes by phase-contrast microscopic observation and NMB staining revealed two different forms of reticulocytes which could be clearly distinguished by their distinctive morphologic appearance [10].

Associations of GPNMB with chemical compounds

• CONCLUSIONS: In conclusion, mivacurium-induced NMB is of very short duration in paediatric patients, and therefore repetitive doses are required to maintain a deep neuromuscular block [11].
• Two children in the mivacurium group and 11 in the vecuronium group required pharmacological reversal of the NMB at the end of surgery (P < 0.01) [11].
• In vitro binding assays indicated that NMB has high affinity for D-2 receptors in primate brain (K1 = 3.6 nM), with a receptor specificity exceeding that of spiperone [12].

Analytical, diagnostic and therapeutic context of GPNMB

• The binding affinity constants of the mAbs ranged from 0.27 x 10(8) to 9.6 x 10(8) M(-1) measured by surface plasmon resonance with immobilized GPNMB, or 1.7 to 2.1 x 10(8) M(-1) by Scatchard analyses with cell-expressed GPNMB [3].
• Increasing expression of Gpnmb mRNA was observed during differentiation of murine primary osteoblast cell cultures [1].
• Patients who underwent inpatient surgery with neuromuscular blockade during a preguideline period (March 1, 1992, through May 31, 1992) or a postguideline period (March 1, 1993, through May 31, 1993) were randomly selected (n = 200 per group) and compared to determine the relative appropriateness, effectiveness, safety, and cost of NMB use [13].

References