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Tmprss3, a Transmembrane Serine Protease Deficient in Human DFNB8/10 Deafness, Is Critical for Cochlear Hair Cell Survival at the Onset of Hearing
- Source :
- Journal of Biological Chemistry, Vol. 286, No 19 (2011) pp. 17383-97, Journal of Biological Chemistry, Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2011, ⟨10.1074/jbc.M110.190652⟩
- Publication Year :
- 2011
- Publisher :
- Elsevier BV, 2011.
-
Abstract
- International audience; Mutations in the type II transmembrane serine protease 3 (TMPRSS3) gene cause non-syndromic autosomal recessive deafness (DFNB8/10), characterized by congenital or childhood onset bilateral profound hearing loss. In order to explore the physiopathology of TMPRSS3 related deafness, we have generated an ethyl-nitrosourea-induced mutant mouse carrying a protein-truncating nonsense mutation in Tmprss3 (Y260X) and characterized the functional and histological consequences of Tmprss3 deficiency. Auditory brainstem response revealed that wild type and heterozygous mice have normal hearing thresholds up to 5 months of age, whereas Tmprss3 Y260X homozygous mutant mice exhibit severe deafness. Histological examination showed degeneration of the organ of Corti in adult mutant mice. Cochlear hair cell degeneration starts at the onset of hearing, postnatal day 12, in the basal turn and progresses very rapidly toward the apex, reaching completion within 2 days. Given that auditory and vestibular deficits often co-exist, we evaluated the balancing abilities of Tmprss3 Y260X mice by using rotating rod and vestibular behavioral tests. Tmprss3 Y260X mice effectively displayed mild vestibular syndrome that correlated histologi-cally with a slow degeneration of saccular hair cells. In situ hybridization in the developing inner ear showed that Tmprss3 mRNA is localized in sensory hair cells in the cochlea and the vestibule. Our results show that Tmprss3 acts as a permissive factor for cochlear hair cells survival and activation at the onset of hearing and is required for saccular hair cell survival. This mouse model will certainly help to decipher the molecular mechanisms underlying DFNB8/10 deafness and cochlear function.
- Subjects :
- Male
Pathology
medicine.medical_specialty
Serine Proteases/chemistry/genetics/metabolism
Cell Survival
Nonsense mutation
Biology
Biochemistry
Hearing/physiology
Mice
03 medical and health sciences
0302 clinical medicine
Hearing
Hair Cells, Auditory
otorhinolaryngologic diseases
medicine
Animals
Humans
ddc:576.5
Inner ear
Molecular Biology
Cochlea
030304 developmental biology
Vestibular system
Mice, Inbred C3H
0303 health sciences
Behavior, Animal
Hair Cells, Auditory/cytology
Cell Membrane/metabolism
Cell Membrane
Membrane Proteins
Molecular Bases of Disease
Cell Biology
Anatomy
medicine.anatomical_structure
Auditory brainstem response
Cochlea/metabolism
Organ of Corti
Vestibule
Mutation
Membrane Proteins/chemistry/genetics
[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
Female
sense organs
Hair cell
Serine Proteases
030217 neurology & neurosurgery
HeLa Cells
Subjects
Details
- ISSN :
- 00219258 and 1083351X
- Volume :
- 286
- Database :
- OpenAIRE
- Journal :
- Journal of Biological Chemistry
- Accession number :
- edsair.doi.dedup.....a1ab4eda59ab3febb748e31e16b4b6e9