Journal article
Characterisation of DRASIC in the mouse inner ear
Hearing research, Vol.190(1), pp.149-160
2004
DOI: 10.1016/S0378-5955(04)00015-2
PMID: 15051137
Abstract
Within the cochlea, the hair cells detect sound waves and transduce them into receptor potential. The molecular architecture of the highly specialised cochlea is complex and until recently little was known about the molecular interactions which underlie its function. It is now clear that the coordinated expression and interplay of hundreds of genes and the integrity of cochlear cells regulate this function. It was hypothesised that transcripts expressed highly or specifically in the cochlea are likely to have important roles in normal hearing. Microarray analyses of the Soares NMIE library, consisting of 1536 cDNA clones isolated from the mouse inner ear, suggested that the expression of the mechanoreceptor DRASIC was enriched in the cochlea compared to other tissues. This amiloride-sensitive ion channel is a member of the DEG/ENaC superfamily and a potential candidate for the unidentified mechanoelectrical transduction channel of the sensory hair cells of the cochlea. The cochlear-enriched expression of amiloride-sensitive cation channel 3 (ACCN3) was confirmed by quantitative real-time polymerase chain reaction. Using in situ hybridisation and immunofluorescence, DRASIC expression was localised to the cells and neural fibre region of the spiral ganglion. DRASIC protein was also detected in cells of the organ of Corti. DRASIC may be present in cochlear hair cells as the ACCN3 transcript was shown to be expressed in immortalised cell lines that exhibit characteristics of hair cells. The normal mouse ACCN3 cDNA and an alternatively spliced transcript were elucidated by reverse transcription polymerase chain reaction from mouse inner ear RNA. This transcript may represent a new protein isoform with an as yet unknown function. A DRASIC knockout mouse model was tested for a hearing loss phenotype and was found to have normal hearing at 2 months of age but appeared to develop hearing loss early in life. The human homologue of ACCN3, acid-sensing ion channel 3, maps to the same chromosomal region as the autosomal recessive hearing loss locus DFNB13. However, we did not detect mutations in this gene in a family with DFNB13 hearing loss.
Details
- Title: Subtitle
- Characterisation of DRASIC in the mouse inner ear
- Creators
- Michael S Hildebrand - Department of Gene Identification and Expression, Murdoch Childrens Research Institute, Royal Children’s Hospital, Flemington Road, Parkville, Vic. 3052, AustraliaMichelle G de Silva - Department of Gene Identification and Expression, Murdoch Childrens Research Institute, Royal Children’s Hospital, Flemington Road, Parkville, Vic. 3052, AustraliaTuomas Klockars - Department of Gene Identification and Expression, Murdoch Childrens Research Institute, Royal Children’s Hospital, Flemington Road, Parkville, Vic. 3052, AustraliaElizabeth Rose - Department of Otolaryngology, University of Melbourne, Royal Children’s Hospital, Melbourne, Vic., AustraliaMargaret Price - Howard Hughes Medical Institute, Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, IA, USARichard J.H Smith - Interdepartmental Genetics PhD Program, Department of Otolaryngology, University of Iowa, Iowa City, IA, USAWyman T McGuirt - Interdepartmental Genetics PhD Program, Department of Otolaryngology, University of Iowa, Iowa City, IA, USAHelen Christopoulos - Department of Gene Identification and Expression, Murdoch Childrens Research Institute, Royal Children’s Hospital, Flemington Road, Parkville, Vic. 3052, AustraliaChristine Petit - Unité de Génétique des Déficits Sensoriels, CNRS URA 1968, Institut Pasteur, Paris, FranceHans-Henrik M Dahl - Department of Gene Identification and Expression, Murdoch Childrens Research Institute, Royal Children’s Hospital, Flemington Road, Parkville, Vic. 3052, Australia
- Resource Type
- Journal article
- Publication Details
- Hearing research, Vol.190(1), pp.149-160
- DOI
- 10.1016/S0378-5955(04)00015-2
- PMID
- 15051137
- NLM abbreviation
- Hear Res
- ISSN
- 0378-5955
- eISSN
- 1878-5891
- Publisher
- Elsevier B.V
- Language
- English
- Date published
- 2004
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Otolaryngology; Internal Medicine
- Record Identifier
- 9984007198302771
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