title: Characterization of a spontaneous, recessive, missense mutation arising in the Tecta gene.
abstract: 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 Tecta(deltaENT)/(deltaENT) mouse. As in the Tecta(deltaENT/(deltaENT) 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.
authors.affiliation: Unidad de Genética Molecular, Hospital Ramón y Cajal, Carretera de Colmenar Km 9, 28034, Madrid, Spain. mmoreno.hrc@salud.madrid.org
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Moreno-Pelayo
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Goodyear
authors.forename: Angeles
authors.initials: A
authors.lastname: Mencía
authors.forename: Silvia
authors.initials: S
authors.lastname: Modamio-Høybjør
authors.forename: P Kevin
authors.initials: PK
authors.lastname: Legan
authors.forename: Leticia
authors.initials: L
authors.lastname: Olavarrieta
authors.forename: Felipe
authors.initials: F
authors.lastname: Moreno
authors.forename: Guy P
authors.initials: GP
authors.lastname: Richardson
mesh_terms: D000818:Animals; D001483:Base Sequence; D004195:Disease Models, Animal; D016326:Extracellular Matrix Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D058851:GPI-Linked Proteins; D005808:Genes, Recessive; D006319:Hearing Loss, Sensorineural / Q000235:genetics* / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D011247:Pregnancy; D013680:Tectorial Membrane / Q000473:pathology / Q000502:physiology
chemical_list: D016326:Extracellular Matrix Proteins; D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins; C105350:Tecta protein, mouse