Cochlear function in mice with only one copy of the prestin gene.
Targeted deletion of the prestin gene reduces cochlear sensitivity and eliminates both frequency selectivity and outer hair cell (OHC) somatic electromotility. In addition, it has been reported by Liberman and colleagues that F2 generation heterozygotes exhibit a 6 dB reduction in sensitivity, as well as a decrease in protein and electromotility. Considering that the active process is non-linear, a halving of somatic electromotility would be expected to produce a much larger change in sensitivity. We therefore re-evaluated comparisons between heterozygotes and wildtype mice using both in vivo and in vitro electrophysiology, as well as molecular biology. Data reported here for F3-F5 generation mice indicate that compound action potential thresholds and tuning curves, as well as the cochlear microphonic, are similar in heterozygotes and wildtype controls. Measurements of non-linear capacitance in isolated OHCs demonstrate that charge density, as well as the voltage dependence and sensitivity of motor function, is indistinguishable in the two genotypes, as is somatic electromotility. In addition, both immunocytochemistry and western blot analysis in young adult mice suggest that prestin protein in heterozygotes is near normal. In contrast, prestin mRNA is always less than in wildtype mice at all ages tested. Results from F3-F5 generation mice suggest that one copy of the prestin gene is capable of compensating for the deleted copy and that heterozygous mice do not suffer peripheral hearing impairment.
Cheatham
M A
MA
Department of Communication Sciences and Disorders, Northwestern University, Evanston, IL 60208-3550, USA. m-cheatham@northwestern.edu
Zheng
J
J
Huynh
K H
KH
Du
G G
GG
Gao
J
J
Zuo
J
J
Navarrete
E
E
Dallos
P
P
D000818:Animals; D001307:Auditory Perception / Q000502:physiology*; D003051:Cochlea / Q000502:physiology*; D017353:Gene Deletion; D018628:Gene Dosage / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D020409:Molecular Motor Proteins; D011506:Proteins / Q000502:physiology*
D020409:Molecular Motor Proteins; C498720:Pres protein, mouse; D011506:Proteins