Bone Abstracts

Optineurin (OPTN) is a protein encoded by the OPTN gene. This protein is involved in several cellular mechanisms such as autophagy, NF-κB signaling, cellular morphogenesis, membrane and vesicle trafficking, and transcription activation. Mutations in OPTN have been described in glaucoma, amyotrophic lateral sclerosis and other neurological diseases. More recently, a polymorphism in this gene was also identified by a genome wide association study to be associated with Paget’s disease of bone (PDB), making OPTN a strong candidate gene to be involved in PDB and bone; however defining the molecular mechanisms by which variants in this gene may contribute to this bone disease requires further studies. Because zebrafish has been validated as a good model to study bone related diseases, the objective of the present work was to evaluate if zebrafish could be a good system to study the molecular mechanisms through which OPTN may contribute to PDB pathogenesis. Through a comparative analysis, we observed that OPTN is encoded by a single copy gene, both in human and zebrafish, and its genomic structure is also conserved. The neighbor genes and chromosomal localization were also maintained, which strongly suggests that zebrafish optn is the ortholog of human OPTN. Bioinformatic analysis indicates that zebrafish and human OPTN seem to be regulated by common transcriptional factors related to bone such as TWIST, KRUEPPEL, LIM domain, NFAT, NF-κB and RXR. Furthermore, OPTN protein comparison between several species revealed a high degree of conservation in the functional domains of the protein and in its 3D structure. In conclusion, this study demonstrates that OPTN is well conserved throughout evolution, and therefore zebrafish, which has been previously validated as a good model to study bone related pathologies, could be considered to further study the biologic role of OPTN in bone diseases and bone development.