Hearing threshold elevation precedes hair-cell loss in prestin knockout mice.
Our previous characterization of prestin knockout (-/-) mice demonstrated that prestin is required for the eletromotility of outer hair cells (OHCs) and for the cochlear amplifier. Because hair-cell loss was observed in the basal 25% of cochleae in adult prestin-/- mice, it remained unclear how hair-cell loss progressed, whether hearing thresholds were elevated, and whether OHCs had normal ultra-structure in young prestin-/- mice. We report here that in prestin-/- mice, no significant hair-cell loss occurred before postnatal day 28 (P28); apoptosis of hair cells began at P28; and the loss of inner hair cells lagged behind that of OHCs. The prestin-/- mice had hearing thresholds that were significantly elevated (by approximately 25 dB) as early as P14; their thresholds at high frequencies were significantly elevated (by approximately 50 dB) at P21. The prestin heterozygous (+/-) mice displayed a significant threshold elevation (approximately 3.5 dB) at P21. In addition, transmission electronic microscopy shown that no obvious abnormality occurs in the sterocilla, lateral wall, tight junction and synapses of the outer hair cells. Our results demonstrate that the absence of prestin, not hair-cell loss, is the primary cause of high-frequency hearing threshold elevation in prestin-/- and +/- mice.
Wu
Xudong
X
Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Gao
Jiangang
J
Guo
Yunkai
Y
Zuo
Jian
J
D000375:Aging / Q000502:physiology; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001309:Auditory Threshold; D016057:Evoked Potentials, Auditory, Brain Stem; D006199:Hair Cells, Auditory, Inner / Q000166:cytology / Q000378:metabolism*; D018072:Hair Cells, Auditory, Outer / Q000378:metabolism* / Q000648:ultrastructure; D006316:Hearing Loss, High-Frequency / Q000473:pathology*; D020287:In Situ Nick-End Labeling; D051379:Mice; D018345:Mice, Knockout; D020409:Molecular Motor Proteins; D011506:Proteins / Q000235:genetics / Q000378:metabolism*
D020409:Molecular Motor Proteins; C498720:Pres protein, mouse; D011506:Proteins