Inner Ears Without Pendrin Expression in the Endolymphatic Sac

The mouse model Foxi1~'~, which lacks expression of the transcription factor FOXI1, expresses pendrin in the cochlea and in the vestibular labyrinth but lacks pendrin expression in the endolymphatic sac (Hulander et al. 2003). The observations that Foxi1~'~ mice are deaf, have vestibular dysfunction, and develop an enlargement of the inner ear point to the importance of the endolymphatic sac for the development of the cochlea and the vestibular labyrinth.

Inner Ear Without Pendrin Expression in the Cochlea and Vestibular Labyrinth

Slc26a4A/A and Slc26a4A/+ mice have been used as genetic background for a model that features a spatially limited pendrin expression (Li et al. 2013a). Tg(B1-hPDS)Slc26a4A/A mice contain a transgene, which consists of the promoter for human ATP6V1B1 that drives the expression of human SLC26A4,

formerly called hPDS. ATP6V1B1 codes for the Bl-subunit of the H+ ATPase, which is expressed in mitochondria-rich cells of the endolymphatic sac but not in the cochlea or in the vestibular labyrinth. Thus, Tg(B1-hPDS)Slc26a4A/A mice express human pendrin in mitochondria-rich cells of the endolymphatic sac but lack pendrin expression in the cochlea and the vestibular labyrinth of the inner ear (Li et al. 2013a). Tg(B1-hPDS)Slc26a4AA mice do not develop the enlargement typically observed in Slc26a4A/A mice. This finding demonstrates that restoration of pendrin expression in the endolymphatic sac is sufficient to restore fluid absorption in the endolymphatic sac and to restore normal fluid homeostasis throughout the inner ear. Most interestingly, hearing and balance are restored in Tg(B1-hPDS)Slc26a4A/A mice. These findings raise the possibility that a spatially limited therapy focused on the endolymphatic sac (a structure that is relatively remote from the cochlea) might restore normal hearing and balance. Although this finding suggests that the expression of pendrin in the cochlea and the vestibular labyrinth is dispensable for hearing and balance, it remains to be determined whether a cochlea without pendrin has a robust hearing phenotype or whether pendrin expression has a protective or homeostatic role in response to common stressors such as noise and aging.

 
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