Inner Ear Morphology Is Perturbed in Two Novel Mouse Models of Recessive Deafness
AuthorMiller, KA; Williams, LH; Rose, E; Kuiper, M; Dahl, H-HM; Manji, SSM
Source TitlePLoS One
PublisherPUBLIC LIBRARY SCIENCE
University of Melbourne Author/sRose, Elizabeth; DAHL, HANS-HENRIK; MANJI, SHEHNAAZ; KUIPER, MICHAEL
Medicine and Radiology
Audiology and Speech Pathology
Document TypeJournal Article
CitationsMiller, K. A., Williams, L. H., Rose, E., Kuiper, M., Dahl, H. -H. M. & Manji, S. S. M. (2012). Inner Ear Morphology Is Perturbed in Two Novel Mouse Models of Recessive Deafness. PLOS ONE, 7 (12), https://doi.org/10.1371/journal.pone.0051284.
Access StatusOpen Access
Human MYO7A mutations can cause a variety of conditions involving the inner ear. These include dominant and recessive non-syndromic hearing loss and syndromic conditions such as Usher syndrome. Mouse models of deafness allow us to investigate functional pathways involved in normal and abnormal hearing processes. We present two novel mouse models with mutations in the Myo7a gene with distinct phenotypes. The mutation in Myo7a(I487N/I487N) ewaso is located within the head motor domain of Myo7a. Mice exhibit a profound hearing loss and manifest behaviour associated with a vestibular defect. A mutation located in the linker region between the coiled-coil and the first MyTH4 domains of the protein is responsible in Myo7a(F947I/F947I) dumbo. These mice show a less severe hearing loss than in Myo7a(I487N/I487N) ewaso; their hearing loss threshold is elevated at 4 weeks old, and progressively worsens with age. These mice show no obvious signs of vestibular dysfunction, although scanning electron microscopy reveals a mild phenotype in vestibular stereocilia bundles. The Myo7a(F947I/F947I) dumbo strain is therefore the first reported Myo7a mouse model without an overt vestibular phenotype; a possible model for human DFNB2 deafness. Understanding the molecular basis of these newly identified mutations will provide knowledge into the complex genetic pathways involved in the maintenance of hearing, and will provide insight into recessively inherited sensorineural hearing loss in humans.
- Click on "Export Reference in RIS Format" and choose "open with... Endnote".
- Click on "Export Reference in RIS Format". Login to Refworks, go to References => Import References