Gentamicin-induced hair cell death is not dependent on the apoptosis receptor Fas.
OBJECTIVE
The hair cells are the most vulnerable elements in the cochlea, and damage to them is the most common cause of sensorineural hearing loss. Understanding the intracellular events that lead to the death of hair cells is a key to developing protective strategies. The Fas death receptor-mediated apoptotic pathway is well studied and plays an important role in the elimination of damaged cells in a number of different cellular systems. We have studied the role of the Fas receptor in aminoglycoside-mediated toxicity in vitro. We employed the MRL/MpJ-Fas mouse, which does not express a functional Fas receptor.


METHODS
Response of Fas-deficient hair cells to gentamicin was compared with the response of normal hair cells in vitro.


METHODS
Basal turn organ of Corti explants from p3-5 mice were maintained in tissue culture and treated with gentamicin for 72 hours. The explants were fixed and were stained with phalloidin, and counting was performed.


RESULTS
There was no difference in hair cell loss between Fas mutant mice and control MRL/MpJ mice with a functional Fas receptor.


CONCLUSIONS
The gentamicin-mediated hair cell death is not dependent on a functional Fas receptor.
Bodmer
Daniel
D
Department of Surgery, Division of Otolaryngology, University of California-San Diego School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Brors
Dominik
D
Pak
Kwang
K
Bodmer
Morana
M
Ryan
Allen F
AF
D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D017209:Apoptosis / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D046508:Culture Techniques; D005839:Gentamicins / Q000009:adverse effects*; D006198:Hair Cells, Auditory / Q000187:drug effects*; D006319:Hearing Loss, Sensorineural / Q000139:chemically induced / Q000473:pathology; D051379:Mice; D019463:Mice, Inbred MRL lpr; D008817:Mice, Mutant Strains; D019014:fas Receptor / Q000187:drug effects*
D000900:Anti-Bacterial Agents; D005839:Gentamicins; D019014:fas Receptor