The Mass1frings mutation underlies early onset hearing impairment in BUB/BnJ mice, a model for the auditory pathology of Usher syndrome IIC
| Autor: | Konrad Noben-Trauth, Qing Yin Zheng, Louis J. Ptáček, Michael D. Weston, K.R. Johnson |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
medicine.medical_specialty
Pathology Ratón Hearing loss Usher syndrome Biology Article Receptors G-Protein-Coupled Mice CDH23 Evoked Potentials Auditory Brain Stem otorhinolaryngologic diseases Genetics medicine Animals Hearing Loss Crosses Genetic Cochlea DNA Primers Electrophoresis Agar Gel Anatomical pathology medicine.disease Mice Mutant Strains Pathophysiology Disease Models Animal medicine.anatomical_structure Mutation Microscopy Electron Scanning Hair cell medicine.symptom Microsatellite Repeats |
| Zdroj: | Genomics. 85:582-590 |
| ISSN: | 0888-7543 |
| DOI: | 10.1016/j.ygeno.2005.02.006 |
| Popis: | The human ortholog of the gene responsible for audiogenic seizure susceptibility in Frings and BUB/BnJ mice (mouse gene symbol Mass1) recently was shown to underlie Usher syndrome type IIC (USH2C). Here we report that the Mass1frings mutation is responsible for the early onset hearing impairment of BUB/BnJ mice. We found highly significant linkage of Mass1 with ABR threshold variation among mice from two backcrosses involving BUB/BnJ mice with mice of strains CAST/EiJ and MOLD/RkJ. We also show an additive effect of the Cdh23 locus in modulating the progression of hearing loss in backcross mice. Together, these two loci account for more than 70% of the total ABR threshold variation among the backcross mice at all ages. The modifying effect of the strain-specific Cdh23ahl variant may account for the hearing and audiogenic seizure differences observed between Frings and BUB/BnJ mice, which share the Mass1frings mutation. During postnatal cochlear development in BUB/BnJ mice, stereocilia bundles develop abnormally and remain immature and splayed into adulthood, corresponding with the early onset hearing impairment associated with Mass1frings. Progressive base-apex hair cell degeneration occurs at older ages, corresponding with the age-related hearing loss associated with Cdh23ahl. The molecular basis and pathophysiology of hearing loss suggest BUB/BnJ and Frings mice as models to study cellular and molecular mechanisms underlying USH2C auditory pathology. |
| Databáze: | OpenAIRE |
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