Characterization of a Spontaneous, Recessive, Missense Mutation Arising in the Tecta Gene

• Published in: Journal of the Association for Research in Otolaryngology 2008-06, Vol.9 (2), p.202-214
• Main Authors: Moreno-Pelayo, Miguel Ángel, Goodyear, Richard J., Mencía, Angeles, Modamio-Høybjør, Silvia, Legan, P. Kevin, Olavarrieta, Leticia, Moreno, Felipe, Richardson, Guy P.
• Format: Article
• Language: English
• Subjects: Animals; Base Sequence; Disease Models, Animal; Extracellular Matrix Proteins - genetics; Extracellular Matrix Proteins - metabolism; Female; Genes, Recessive; GPI-Linked Proteins; Hearing Loss, Sensorineural - genetics; Hearing Loss, Sensorineural - pathology; Male; Medicine; Medicine & Public Health; Membrane Glycoproteins - genetics; Membrane Glycoproteins - metabolism; Mice; Molecular Sequence Data; Mutation, Missense; Neurobiology; Neurosciences; Otorhinolaryngology; Pedigree; Phenotype; Pregnancy; Tectorial Membrane - pathology; Tectorial Membrane - physiology
• ISSN: 1525-3961; 1438-7573
• DOI: 10.1007/s10162-008-0116-0

The TECTA gene encodes alpha-tectorin (TECTA), a major noncollagenous component of the tectorial membrane (TM). In humans, mutations in TECTA lead to either dominant (DFNA8/A12) or recessive (DFNB21) forms of nonsyndromic hearing loss. All missense mutations in TECTA that have been reported thus far are associated with the dominant subtype, whereas those leading to recessive deafness are all inactivating mutations. In this paper, we characterize a spontaneous missense mutation (c.1046C > A, p.A349D) arising in the mouse Tecta gene that is, unlike all previously reported missense mutations in TECTA , recessive. The morphological phenotype of the Tecta A349D/A349D mouse resembles but is not identical to that previously described for the mouse. As in the mouse, the TM is completely detached from the surface of the organ of Corti and spiral limbus, lacks a striated-sheet matrix, and is deficient in both beta-tectorin (Tectb) and otogelin. A significant amount of Tecta is, however, detected in the TM of the Tecta A349D/A349D mouse, and numerous, electron-dense matrix granules are seen interspersed among the disorganized collagen fibrils. Mutated Tecta A349D is therefore incorporated into the TM but presumably unable to interact with either Tectb or otogelin. The Tecta A349D/A349D mouse reveals that missense mutations in Tecta can be recessive and lead to TM detachment and suggests that should similar mutations arise in the human population, they would likely cause deafness.