Hearing loss in the laminin-deficient dy mouse model of congenital muscular dystrophy.
Sensorineural hearing loss is found in many inherited forms of muscular dystrophy. We investigated the dy mouse model, which has congenital muscular dystrophy due to a defect in laminin alpha 2, for evidence of cochlear dysfunction. Auditory brainstem response (ABR) audiometry to pure tones was used to evaluate 3-month-old homozygous dy/dy and age-matched C57 control mice. The average ABR thresholds to tone-burst stimuli for four frequencies (4, 8, 16, and 32 kHz) were determined and statistically compared by ANOVA. The dy/dy mice demonstrated elevated auditory thresholds ranging from 25 to 27 dB at each frequency tested (p<0.0001). Anatomic evaluations of the ears revealed pathology ranging from extensive connective tissue infiltration within the inner ear to possible minor defects in the cells of the organ of Corti. These anatomic and physiologic observations suggest that the extracellular matrix protein laminin plays a crucial role in normal cochlear function. Furthermore, the dy congenital muscular dystrophy mouse offers a novel model for evaluation of sensorineural hearing loss associated with muscular dystrophy.
Department of Pediatrics, Oregon Retinal Degeneration Center, Oregon Child Health Research Center, Doernbecher Children's Hospital, Oregon Health Sciences University, 3181 S.W. Sam Jackson Park Road, Portland, OR 97201-3042, USA. pillersd@ohsu.edu
De-Ann M
DA
Pillers
J Beth
JB
Kempton
Nancy M
NM
Duncan
Jiaqing
J
Pang
Shannon J
SJ
Dwinnell
Dennis R
DR
Trune
D000818:Animals; D001933:Brain Stem / Q000503:physiopathology; D004195:Disease Models, Animal; D007758:Ear, Inner / Q000033:anatomy & histology; D006319:Hearing Loss, Sensorineural / Q000235:genetics* / Q000503:physiopathology; D007797:Laminin / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009136:Muscular Dystrophies / Q000151:congenital / Q000235:genetics* / Q000503:physiopathology
D007797:Laminin