Normal cochlear function in mdx and mdx(Cv3) Duchenne muscular dystrophy mouse models.
OBJECTIVE
Sensorineural hearing loss has been found in association with inherited muscular dystrophies in humans and in mouse models. An increased brainstem auditory evoked response threshold has been previously reported in the dystrophin-deficient mdx mouse model for Duchenne muscular dystrophy, suggesting that full-length dystrophin (Dp427) is involved in hearing. The objective of the present study was to confirm cochlear dysfunction with this gene defect and determine whether the shorter carboxyl terminus isoforms of dystrophin are also critical in maintaining normal hearing.


METHODS
Case controlled. Animal model.


METHODS
Auditory brainstem response (ABR) audiometry to pure tones was used to evaluate cochlear function. Fourteen mdx, 4 mdx(Cv3), and 13 age-matched control (C57BL/6J and C57BL/10ScSn) male mice were tested at 5 weeks and 11 weeks of age. The ABR thresholds to tone-burst stimuli at 4, 8, 16, and 32 kHz were obtained for each ear and statistically compared (ANOVA) for potential group differences.


RESULTS
Both mdx and mdx(Cv3) mice demonstrated normal ABR thresholds when compared with controls.


CONCLUSIONS
Both mdx and mdx(Cv3) mouse models have normal hearing by ABR. The authors' data suggest that dystrophin and its carboxyl terminus isoforms do not play a critical role in hearing in the mouse. This was unexpected, as previous studies using the brainstem auditory evoked response method suggested that the mdx mouse has an increased threshold for hearing.
Pillers
D A
DA
Department of Pediatrics, Oregon Child Health Research Center, Doernbecher Children's Hospital, Oregon Health Sciences University, Portland 97201-3042, USA. pillersd@ohsu.edu
Duncan
N M
NM
Dwinnell
S J
SJ
Rash
S M
SM
Kempton
J B
JB
Trune
D R
DR
D000818:Animals; D001309:Auditory Threshold; D016022:Case-Control Studies; D003051:Cochlea / Q000502:physiology*; D004195:Disease Models, Animal; D016189:Dystrophin / Q000172:deficiency* / Q000235:genetics; D005072:Evoked Potentials, Auditory; D016057:Evoked Potentials, Auditory, Brain Stem; D005838:Genotype; D006309:Hearing / Q000502:physiology; D006319:Hearing Loss, Sensorineural / Q000175:diagnosis; D008297:Male; D051379:Mice; D018101:Mice, Inbred mdx; D009137:Muscular Dystrophy, Animal / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology*; D020033:Protein Isoforms
D016189:Dystrophin; D020033:Protein Isoforms