Muscular dystrophy mouse models and congenital sensorineural hearing deficits: Implication of muscle proteins in function of inner ear

D. M. Pillers, N. M. Duncan, S. M. Rash, S. J. Dwinnell, J. B. Kempton, Dennis Trune

Research output: Contribution to journalArticle

Abstract

Purpose: Sensorineural hearing loss is found in many inherited forms of muscular dystrophy. Hearing loss has also been reported in the X-linked muscular dystrophy mouse model mdx that lacks dystrophin (the protein defective in Duchenne muscular dystrophy (DMD)). We have been investigating non-muscle manifestations of DMD in a panel of mdx mice with allelic mutations of dystrophin and have shown that some non-muscle manifestations are linked to abnormal expression of carboxy terminus isoforms of dystrophin. To determine whether a specific isoform was implicated in the hearing abnormalities, we studied mdxCr3 mice with a 3′ mutation of dystrophin and in whom all known dystrophin isoforms are absent. For comparison, we studied the mdx strain with a 5′ mutation of dystrophin and in whom only full-length dystrophin is disrupted. In addition, to investigate other proteins associated with dystrophin we investigated the dy/dy mouse that is defective in laminin expression and has a severe muscular dystrophy phenotype. Laminin interfaces between the extracellular matrix and dystrophin via the transmembrane dystrophin-associated-glycoprotein complex. Methods: Auditory brainstem response (ABR) audiometry to pure tones was used to evaluate cochlear function. 10 mdx, 4 mdxCv3, 6 dy/dy, and 16 age-matched C57BL/6J control mice were studied. Animals were anesthetized and both ears of each mouse were stimulated separately with a closed tube sound delivery system at frequencies of 4,8,16, and 32 kHz. The average threshold for each group was determined for each frequency and statistically compared with a two-way ANOVA to determine differences in auditory function. Results: mdx and mdxCv3 showed no statistical difference in ABR thresholds as compared 13 controls. The dy/dy mice demonstrated elevated auditory thresholds at all frequencies tested. The increasec thresholds ranged from 17 to 25 dB across the four frequencies with p

Original languageEnglish (US)
JournalInvestigative Ophthalmology and Visual Science
Volume37
Issue number3
StatePublished - Feb 15 1996

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Dystrophin
Muscle Proteins
Muscular Dystrophies
Inner Ear
Hearing
Inbred mdx Mouse
Protein Isoforms
Duchenne Muscular Dystrophy
Brain Stem Auditory Evoked Potentials
Laminin
Mutation
Dystrophin-Associated Proteins
Auditory Threshold
Pure-Tone Audiometry
Sensorineural Hearing Loss
Cochlea
Hearing Loss
Extracellular Matrix
Ear
Glycoproteins

ASJC Scopus subject areas

  • Ophthalmology

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Muscular dystrophy mouse models and congenital sensorineural hearing deficits : Implication of muscle proteins in function of inner ear. / Pillers, D. M.; Duncan, N. M.; Rash, S. M.; Dwinnell, S. J.; Kempton, J. B.; Trune, Dennis.

In: Investigative Ophthalmology and Visual Science, Vol. 37, No. 3, 15.02.1996.

Research output: Contribution to journalArticle

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abstract = "Purpose: Sensorineural hearing loss is found in many inherited forms of muscular dystrophy. Hearing loss has also been reported in the X-linked muscular dystrophy mouse model mdx that lacks dystrophin (the protein defective in Duchenne muscular dystrophy (DMD)). We have been investigating non-muscle manifestations of DMD in a panel of mdx mice with allelic mutations of dystrophin and have shown that some non-muscle manifestations are linked to abnormal expression of carboxy terminus isoforms of dystrophin. To determine whether a specific isoform was implicated in the hearing abnormalities, we studied mdxCr3 mice with a 3′ mutation of dystrophin and in whom all known dystrophin isoforms are absent. For comparison, we studied the mdx strain with a 5′ mutation of dystrophin and in whom only full-length dystrophin is disrupted. In addition, to investigate other proteins associated with dystrophin we investigated the dy/dy mouse that is defective in laminin expression and has a severe muscular dystrophy phenotype. Laminin interfaces between the extracellular matrix and dystrophin via the transmembrane dystrophin-associated-glycoprotein complex. Methods: Auditory brainstem response (ABR) audiometry to pure tones was used to evaluate cochlear function. 10 mdx, 4 mdxCv3, 6 dy/dy, and 16 age-matched C57BL/6J control mice were studied. Animals were anesthetized and both ears of each mouse were stimulated separately with a closed tube sound delivery system at frequencies of 4,8,16, and 32 kHz. The average threshold for each group was determined for each frequency and statistically compared with a two-way ANOVA to determine differences in auditory function. Results: mdx and mdxCv3 showed no statistical difference in ABR thresholds as compared 13 controls. The dy/dy mice demonstrated elevated auditory thresholds at all frequencies tested. The increasec thresholds ranged from 17 to 25 dB across the four frequencies with p",
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