Slc26a4-insufficiency causes fluctuating hearing loss and stria vascularis dysfunction.
Neurobiol Dis
; 66: 53-65, 2014 Jun.
Article
de En
| MEDLINE
| ID: mdl-24561068
ABSTRACT
SLC26A4 mutations can cause a distinctive hearing loss phenotype with sudden drops and fluctuation in patients. Existing Slc26a4 mutant mouse lines have a profound loss of hearing and vestibular function, with severe inner ear malformations that do not model this human phenotype. In this study, we generated Slc26a4-insufficient mice by manipulation of doxycycline administration to a transgenic mouse line in which all Slc26a4 expression was under the control of doxycycline. Doxycycline was administered from conception to embryonic day 17.5, and then it was discontinued. Auditory brainstem response thresholds showed significant fluctuation of hearing loss from 1 through 3months of age. The endocochlear potential, which is required for inner ear sensory cell function, correlated with auditory brainstem response thresholds. We observed degeneration of stria vascularis intermediate cells, the cells that generate the endocochlear potential, but no other abnormalities within the cochlea. We conclude that fluctuations of hearing result from fluctuations of the endocochlear potential and stria vascularis dysfunction in Slc26a4-insufficient mouse ears. This model can now be used to test potential interventions to reduce or prevent sudden hearing loss or fluctuation in human patients. Our strategy to generate a hypomorphic mouse model utilizing the tet-on system will be applicable to other diseases in which a hypomorphic allele is needed to model the human phenotype.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Strie vasculaire
/
Transporteurs d'anions
/
Perte d'audition
Type d'étude:
Etiology_studies
Limites:
Animals
Langue:
En
Journal:
Neurobiol Dis
Sujet du journal:
NEUROLOGIA
Année:
2014
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique