Pendrin Expression Is Required During a Critical Time Period During Development

The mouse model Tg[E,Tg[RSlc26a4AIA was used to determine the time period during which pendrin expression is required for normal cochlear development (Choi et al. 2011). Mice developed normal hearing, when doxycycline was administered from conception onward. Normal hearing thresholds developed even when the normal onset of pendrin expression at E11.5 was delayed by 5 days to E16.5 in the conditional mutant mice. Further, mice developed normal hearing thresholds, when pendrin expression was terminated by withdrawal of doxycycline as early as P2. These data define E16.5 to P2 as the most critical time period during which pendrin is needed for the development of normal hearing thresholds (Choi et al. 2011). The time period needed for the development of an uncompromised endocochlear potential and a normal endolymphatic pH begin earlier and last longer, which may imply that the hearing phenotype may be less robust in spite of normal thresholds when pendrin expression is restricted to the most critical time period (Choi et al. 2011). Taken together, the observations open the prospect that a temporally limited therapy focused on the prenatal phase of development may restore hearing in individuals bearing mutations of SLC26A4.

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