Hearing loss in a mouse model of Muenke syndrome
Open accessAbstract
The heterozygous Pro250Arg substitution mutation in fibroblast growth factor receptor 3 (FGFR3), which increases ligand-dependent signalling, is the most common genetic cause of craniosynostosis in humans and defines Muenke syndrome. Since FGF signalling plays dosage-sensitive roles in the differentiation of the auditory sensory epithelium, we evaluated hearing in a large group of Muenke syndrome subjects, as well as in the corresponding mouse model (Fgfr3(P244R)). The Muenke syndrome cohort showed significant, but incompletely penetrant, predominantly low-frequency sensorineural hearing loss, and the Fgfr3(P244R) mice showed dominant, fully penetrant hearing loss that was more severe than that in Muenke syndrome individuals, but had the same pattern of relative high-frequency sparing. The mouse hearing loss correlated with an alteration in the fate of supporting cells (Deiters'-to-pillar cells) along the entire length of the cochlear duct, with the most extreme abnormalities found at the apical or low-frequency end. In addition, there was excess outer hair cell development in the apical region. We conclude that low-frequency sensorineural hearing loss is a characteristic feature of Muenke syndrome and that the genetically equivalent mouse provides an excellent model that could be useful in testing hearing loss therapies aimed at manipulating the levels of FGF signalling in the inner ear.
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Low frequency hearing loss is an important complication of Muenke syndrome, requiring hearing aids in about 20% of patients.
“An important complication is low frequency hearing loss, requiring the fitting of hearing aids in B20% of patients.23”
From Craniosynostosis (2011) · cites this paper as [23]
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- Authors
- Mansour, S. L., Twigg, S. R. F., Freeland, R. M., Wall, S. A., Li, C., & Wilkie, A. O. M.
- Affiliations
- University of Utah (US)
- John Radcliffe Hospital (GB)
- Corresponding author
- Mansour, Suzanne L.
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2008-09-25
- Volume
- 18
- Issue
- 1
- Pages
- 43-50
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- PMC
- PMC2644644
- OpenAlex
- W2118531535
- Cited by
- 65
- References
- 50
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 2 · 2023: 1 · 2022: 2 · 2021: 3 · 2020: 3 · 2019: 5 · 2018: 1 · 2017: 3 · 2016: 5 · 2015: 4 · 2014: 5 · 2013: 5 · 2012: 5
- FWCI
- 2.39
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Human Molecular Genetics (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Wellcome Trust (078666)
- National Institute on Deafness and Other Communication Disorders (R01DC002043)
- Topics
- Life Sciences › Neuroscience › Sensory Systems › Hearing, Cochlea, Tinnitus, Genetics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Craniofacial Disorders and Treatments
- Health Sciences › Medicine › Genetics › Congenital Ear and Nasal Anomalies
- Keywords
- Muenke syndrome, sensorineural hearing loss, FGF receptor 3, craniosynostosis, mouse model, cochlear supporting cells, Deiters' cells, pillar cells, outer hair cells, FGF signaling, inner ear development, low-frequency hearing loss
- MeSH terms
- Animals, Disease Models, Animal, Female, Hair Cells, Auditory, Hearing Tests, Humans, Ear, Inner, Male, Mice, Inbred Strains, Mice, Transgenic, Cohort Studies, Signal Transduction, Amino Acid Substitution, Hearing Loss, Mice, Receptor, Fibroblast Growth Factor, Type 3
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