RT Journal Article
SR Electronic
T1 Hair Cell Overexpression of Islet1 Reduces Age-Related and Noise-Induced Hearing Loss
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 15086
OP 15094
DO 10.1523/JNEUROSCI.1489-13.2013
VO 33
IS 38
A1 Mingqian Huang
A1 Albena Kantardzhieva
A1 Deborah Scheffer
A1 M. Charles Liberman
A1 Zheng-Yi Chen
YR 2013
UL http://www.jneurosci.org/content/33/38/15086.abstract
AB Isl1 is a LIM-homeodomain transcription factor that is critical in the development and differentiation of multiple tissues. In the mouse inner ear, Isl1 is expressed in the prosensory region of otocyst, in young hair cells and supporting cells, and is no longer expressed in postnatal auditory hair cells. To evaluate how continuous Isl1 expression in postnatal hair cells affects hair cell development and cochlear function, we created a transgenic mouse model in which the Pou4f3 promoter drives Isl1 overexpression specifically in hair cells. Isl1 overexpressing hair cells develop normally, as seen by morphology and cochlear functions (auditory brainstem response and otoacoustic emissions). As the mice aged to 17 months, wild-type (WT) controls showed the progressive threshold elevation and outer hair cell loss characteristic of the age-related hearing loss (ARHL) in the background strain (C57BL/6J). In contrast, the Isl1 transgenic mice showed significantly less threshold elevation with survival of hair cells. Further, the Isl1 overexpression protected the ear from noise-induced hearing loss (NIHL): both ABR threshold shifts and hair cell death were significantly reduced when compared with WT littermates. Our model suggests a common mechanism underlying ARHL and NIHL, and provides evidence that hair cell-specific Isl1 expression can promote hair cell survival and therefore minimize the hearing impairment that normally occurs with aging and/or acoustic overexposure.