HGNC Approved Gene Symbol: OTOR
Cytogenetic location: 20p12.1 Genomic coordinates (GRCh38) : 20:16,748,358-16,752,164 (from NCBI)
During large-scale analysis of human fetal cochlea EST sequences, Robertson et al. (2000) identified a novel gene, designated OTOR. They also isolated orthologous genes in mouse, chicken, and bullfrog by screening inner ear cDNA libraries. Rendtorff et al. (2001) independently identified OTOR, which they called MIA-like (MIAL), during a search for cochlea-specific EST clusters. Cohen-Salmon et al. (2000) cloned the mouse Otor gene, which they called fibrocyte-derived protein (Fdp), using a subtracted mouse cochlea cDNA library and 5-prime RACE. Human OTOR encodes a 128-amino acid protein with a predicted secretion signal peptide. The protein shares high sequence identity with the mouse (90%), chicken (80%), and bullfrog (60%) orthologs and with the related human CDRAP/MIA protein (601340) (43%). By expressing OTOR in mammalian cell cultures, Rendtorff et al. (2001) showed that OTOR is translated as an approximately 15-kD polypeptide that is assembled into a covalently linked homodimer, modified by sulfation, and secreted from the cells via the Golgi apparatus. By Northern blot analysis, Robertson et al. (2000) detected expression of a major 1.1-kb and minor 1.8- and 4-kb OTOR transcripts in human cochlea. Using RT-PCR and in situ hybridization, Rendtorff et al. (2001) detected OTOR expression specific to a cell layer beneath the sensory epithelium of cochlea and vestibule of human fetal inner ear.
Using in situ hybridization on chicken cochlear sections, Robertson et al. (2000) detected Otor in extracellular matrix areas that support adjacent sensory hair cells. These regions of the chicken cochlea are analogous to the mammalian spiral limbus, osseous spiral lamina, and spiral ligament. Using RT-PCR, Cohen-Salmon et al. (2000) detected mouse Otor expression in the cochlea, with weak expression in eyes, cartilage, and brain. They detected embryonic expression from E10.5 onward in the mesenchyme surrounding the otic epithelium. By in situ hybridization, they detected Otor expression at E17.5 in the fibrocytes surrounding the cochlear and vestibular duct. After birth, expression was detected in all types of fibrocytes in the spiral ligament behind the stria vascularis.
Cohen-Salmon et al. (2000) treated microdissected cultures with Otor antisense oligonucleotides which resulted in a significant reduction in chondrogenesis. They concluded that Otor may play a role in the early chondrogenesis of the periotic mesenchyme and may be a candidate for forms of deafness associated with malformations of the otic capsule.
Rendtorff et al. (2001) and Cohen-Salmon et al. (2000) found that the OTOR gene contains 4 exons spanning approximately 3 kb of genomic DNA.
Rendtorff et al. (2001) reported a frequent polymorphism in the translation initiation codon of OTOR (ACG instead of ATG). Of 505 unrelated individuals analyzed, 9.5% were ACG/ATG heterozygous. The ACG allele failed to direct synthesis of the OTOR protein in transfected cells. Rendtorff et al. (2001) concluded that OTOR may contribute to inner ear dysfunction in humans.
By FISH, Robertson et al. (2000) localized the OTOR gene to chromosome 20p11.23-p12.1. Robertson et al. (2000) and Rendtorff et al. (2001) identified the OTOR sequence in a human genomic clone mapped to chromosome 20p11.22-p12.2. Using STS sequence analysis, Cohen-Salmon et al. (2000) localized OTOR to chromosome 20p11. By interspecific backcross analysis, Cohen-Salmon et al. (2000) localized the mouse Otor gene to a region of syntenic homology on chromosome 2.
Cohen-Salmon, M., Frenz, D., Liu, W., Verpy, E., Voegeling, S., Petit, C. Fdp, a new fibrocyte-derived protein related to MIA/CD-RAP, has an in vitro effect on the early differentiation of the inner ear mesenchyme. J. Biol. Chem. 275: 40036-40041, 2000. [PubMed: 10998416] [Full Text: https://doi.org/10.1074/jbc.M002876200]
Rendtorff, N. D., Frodin, M., Attie-Bitach, T., Vekemans, M., Tommerup, N. Identification and characterization of an inner ear-expressed human melanoma inhibitory activity (MIA)-like gene (MIAL) with a frequent polymorphism that abolishes translation. Genomics 71: 40-52, 2001. [PubMed: 11161796] [Full Text: https://doi.org/10.1006/geno.2000.6409]
Robertson, N. G., Heller, S., Lin, J. S., Resendes, B. L., Weremowicz, S., Denis, C. S., Bell, A. M., Hudspeth, A. J., Morton, C. C. A novel conserved cochlear gene, OTOR: identification, expression analysis, and chromosomal mapping. Genomics 66: 242-248, 2000. [PubMed: 10873378] [Full Text: https://doi.org/10.1006/geno.2000.6224]