| 1998 |
OC90 (otoconin-90) is the major protein component of murine otoconia and contains two domains homologous to secretory phospholipase A2 (sPLA2). The gene is specifically expressed in the developing mouse otocyst, and the mature mouse OC90 is composed of 453 residues. |
cDNA cloning, sequence analysis, and in situ hybridization showing otocyst-specific expression |
Proceedings of the National Academy of Sciences of the United States of America |
High |
9860971
|
| 2007 |
OC90 is essential for formation of the organic matrix of otoconia by specifically recruiting other matrix components including otolin. In Oc90 null mice, the organic matrix fails to form properly, leading to absent/reduced otoconia; the organic matrix forms prior to CaCO3 deposition and controls otoconia growth and morphology by embedding crystallites during seeding and growth. |
Gene targeting (Oc90 knockout mice), protein analysis, histological and ultrastructural examination |
Developmental biology |
High |
17300776
|
| 2008 |
Oc90 deletion leads to formation of giant otoconia (not absent otoconia), causing vestibular imbalance but normal hearing as measured by auditory brainstem responses and otoacoustic emissions. The remnant otoconia mass in Oc90 null mice is still capable of stimulating gravity receptor organs. |
Behavioral balance tests (righting reflex, rotorod, beam-crossing, gait), vestibular evoked potentials (VsEPs), auditory brainstem responses (ABRs), distortion products of otoacoustic emissions (DPOAEs) |
Neuroscience |
High |
18355969
|
| 2008 |
Otoc1, the zebrafish ortholog of OC90, is expressed in the ear between 15–72 hpf and is required for otolith mineralization; morpholino knockdown of otoc1 mRNA translation produces aberrant otolith phenotypes, suggesting Otoc1 nucleates calcium carbonate mineralization of aragonitic otoliths. |
In situ hybridization, antisense morpholino knockdown in zebrafish |
Developmental neurobiology |
Medium |
18000829
|
| 2010 |
Recombinant OC90 facilitates nucleation of calcite crystals and inhibits crystal growth in a concentration-dependent manner in vitro, and induces morphologic changes characteristic of native otoconia. Homology modeling of the sPLA2-like domains of OC90 indicates that a surface of anionic clusters formed upon tertiary folding compensates for the lower density of acidic residues in the primary sequence. |
In vitro calcite crystal growth assay with recombinant OC90, HR-SEM, homology modeling |
Hearing research |
Medium |
20595020
|
| 2010 |
In Oc90 null otoconia, Sparc-like 1 (Sc1/hevin) is drastically upregulated as a compensatory matrix protein. Stable transfection of full-length Oc90 or Sc1 expression constructs in NIH/3T3 cells promotes matrix calcification, demonstrating a direct role for OC90 in driving calcification. |
Protein analysis of Oc90 null vs. wildtype otoconia, stable transfection of NIH/3T3 cells with calcification assay |
Developmental dynamics |
Medium |
20803598
|
| 2011 |
OC90 binds otolin through both the TH and C1q domains of otolin, with full-length otolin showing the strongest interaction. OC90 recruits otolin to the crystal matrix and sequesters Ca2+ in the luminal matrices of the utricle and saccule; absence of OC90 in null mice leads to drastically reduced matrix Ca2+. In vitro, co-expression of OC90 and otolin has a synergistic effect on calcification. |
Co-immunoprecipitation/binding assay, in vivo Ca2+ measurements (utricle/saccule enrichment), cell culture calcification assay, molecular modeling |
PloS one |
High |
21655225
|
| 2011 |
Recombinant otoconin-22 (rOC22, a related sPLA2-like otoconin) selects calcite over aragonite in vitro; alternate folding produces vaterite. Molecular models of OC90 show a surface of uniform negative electrostatic potential proposed to enable localized supersaturation. OC90 is proposed to interact with Otolin in formation of iso-oriented columns of nano-crystallites. |
In vitro crystal growth, circular dichroism, HR-SEM, micro-Raman, molecular modeling |
Acta oto-laryngologica |
Medium |
21401448
|
| 2014 |
OC90 modulates in vitro calcite crystal morphology; coadministration of OC90 and Otolin-1 produces synergistic effects on crystal morphology contributing to otoconia-like shape. OC90 films on mica significantly reduce the interfacial energy for heterogeneous calcite nucleation compared to bulk solution, and OC90 possesses negative surface charge that correlates inversely with interfacial energy. |
In vitro calcium carbonate crystal growth, rotary shadowing, atomic force microscopy (AFM), scanning electron microscopy, zeta potential measurements |
PloS one |
High |
24748133 25709560
|
| 2019 |
In zebrafish pks1 mutants that lack otoliths, OC90 expression within the otocyst is diffuse rather than localized, demonstrating that proper OC90 localization is not sufficient for otolith biomineralization in the absence of pks1, and that additional factors beyond OC90 are required for otolith nucleation. |
Genetic mutant analysis (pks1 loss-of-function), immunofluorescence/in situ hybridization for OC90 localization in zebrafish |
Mechanisms of development |
Medium |
30974150
|
| 2021 |
OC90 and NADPH oxidase Nox3 are functionally cooperative: double heterozygous Oc90/Nox3 mice display severe imbalance and otoconia defects (while single heterozygotes are normal), and cells stably co-expressing both proteins show much greater calcification than cells expressing either alone, indicating that OC90 and Nox3 augment each other's function in otoconia formation and hair bundle maintenance. |
Double heterozygous/null mouse genetics, behavioral and electrophysiological analysis, stable transfection calcification assay |
Journal of vestibular research |
Medium |
33554930
|
| 2021 |
Estrogen receptor (ER) and estrogen-related receptor α (ERRα) interact with each other and cooperatively regulate OC90 expression in rat utricles; bilateral ovariectomy reduces ERRα levels and loosens otoliths, an effect reversed by E2 supplementation. |
Co-immunoprecipitation (ER–ERRα interaction), Western blotting and qPCR for OC90 expression, ovariectomy rat model, scanning electron microscopy of otolith morphology |
Current medical science |
Medium |
34403090
|