Mouse model of enlarged vestibular aqueducts defines temporal requirement of Slc26a4 expression for hearing acquisition

摘要: Mutations in human SLC26A4 are a common cause of hearing loss associated with enlarged vestibular aqueducts (EVA). encodes pendrin, an anion-base exchanger expressed inner ear epithelial cells that secretes HCO3- into endolymph. Studies Slc26a4-null mice indicate pendrin is essential for development, but have not revealed whether specifically necessary homeostasis. profoundly deaf, severe malformations and degenerative changes do model the less phenotype. Here, we describe studies which generated binary transgenic mouse line Slc26a4 expression could be induced doxycycline. The transgenes were crossed onto background so all functional was derived from transgenes. Varying temporal E16.5 to P2 critical interval required acquisition normal hearing. Lack during this period led endolymphatic acidification, endocochlear potential, failure acquire Doxycycline initiation at E18.5 or discontinuation E17.5 resulted partial approximating EVA auditory These data collectively provide mechanistic insight caused by mutations establish further EVA-associated loss.