Biomedical subjects

Tuomas Klockars

Publications and source records attributed to Tuomas Klockars.

7 recordsLinked to original sources

PubMed2007

Inheritance of Meniere's disease in the Finnish population.

OBJECTIVE: To study the inheritance of Ménière's disease in the Finnish population. DESIGN: A detailed questionnaire was sent to patients with symptoms resembling Ménière's disease previously examined at the Department of Otorhinolaryngology, Helsinki University Central Hospital, Finland. PATIENTS: The study population comprised 118 patients with symptoms resembling Ménière's disease. The patients were divided into groups based on the diagnostic criteria by the Committee on Hearing and Equilibrium of the American Academy of Otolaryngology-Head and Neck Surgery. MAIN OUTCOME MEASURES: Relatives with Ménière's disease, geographic distribution of birthplaces of grandparents, symptoms, vestibular findings, and audiologic and otoneurologic tests. RESULTS: Approximately 15% of the patients with definite Ménière's disease were found to represent familial disease. The majority of these patients were female, and they had more severe and intense attacks compared with patients with sporadic Ménière's disease. The mode of inheritance is autosomal dominant with incomplete penetrance. CONCLUSIONS: A significant part of Ménière's disease is inherited. The use of genetic isolates in which genetic homogeneity can be assumed might lead to the identification of gene defects leading to Ménière's disease.

Female↗

PubMed2006

Case report: Meniere's disease and otosclerosis--different outcomes of the same disease?

The etiologies of Meniere's disease and otosclerosis are largely unknown. An association between these two diseases has been proposed on both a clinical and histopathologic basis but the causal relationship is controversial. In this paper we report two families in which both otosclerosis and Meniere's disease are inherited as independent phenotypes suggesting that the two diseases represent different outcomes of the same mutation. Thus the Meniere's disease occasionally seen in otosclerotic patients might not be caused by otosclerosis, but rather by a molecular defect leading to endolymphatic hydrops and/or clinical otosclerosis.

Aged↗

PubMed2006

Molecular characterization and expression of maternally expressed gene 3 (Meg3/Gtl2) RNA in the mouse inner ear.

The pathways responsible for sound perception in the cochlea involve the coordinated and regulated expression of hundreds of genes. By using microarray analysis, we identified several transcripts enriched in the inner ear, including the maternally expressed gene 3 (Meg3/Gtl2), an imprinted noncoding RNA. Real-time PCR analysis demonstrated that Meg3/Gtl2 was highly expressed in the cochlea, brain, and eye. Molecular studies revealed the presence of several Meg3/Gtl2 RNA splice variants in the mouse cochlea, brain, and eye. In situ hybridizations showed intense Meg3/Gtl2 RNA staining in the nuclei of type I spiral ganglion cells and in cerebellum near the dorsal vestibular region of the cochlea. In embryonic mouse head sections, Meg3/Gtl2 RNA expression was observed in the otocyst, brain, eye, cartilage, connective tissue, and muscle. Meg3/Gtl2 RNA expression increased in the developing otocyst and localized to the spiral ganglion, stria vascularis, Reissner's membrane, and greater epithelial ridge (GER) in the cochlear duct. RT-PCR analysis performed on cell lines derived from the organ of Corti, representing neural, supporting, and hair cells, showed significantly elevated levels of Meg3/Gtl2 expression in differentiated neural cells. We propose that Meg3/Gtl2 RNA functions as a noncoding regulatory RNA in the inner ear and that it plays a role in pattern specification and differentiation of cells during otocyst development, as well as in the maintenance of a number of terminally differentiated cochlear cell types.

Animals↗

PubMed2006

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Journal Article↗

PubMed2005

Expression of the carrier protein apolipoprotein D in the mouse inner ear.

The cochlear portion of the inner ear converts movements produced by sound waves into electrical impulses. Transcripts enriched in the cochlea are likely to have an important role in hearing. In this paper, we report that microarray analyses of the Soares NMIE inner ear library revealed cochlear enriched expression of apolipoprotein D (apoD), a glycoprotein and member of the lipocalin family that transport small hydrophobic ligands. The cochlear enriched expression of Apod was validated by quantitative real time PCR analysis. To investigate the function of apoD in the inner ear the transcript and protein were localised in the cochlea. Apod messenger RNA (mRNA) expression was localised to the spiral ligament and spiral limbus, particularly in the suprastrial and supralimbral regions. The apoD protein was detected in the spiral ligament, spiral limbus and also in the outer hair cells of the organ of Corti. Investigation of cell lines exhibiting characteristics of hair and supporting cells revealed no Apod mRNA expression in these cells. This suggests transport of the protein within the cochlea, followed by internalisation into outer hair cells. The spiral limbus and ligament contain subpopulations of fibrocytes that are intimately involved in regulation of ion balance in the cochlear fluids and type I, II and III fibrocytes of the spiral ligament were all shown to be positive for apoD protein. On the basis of these results it was hypothesised that apoD could be involved in maintaining cochlear fluid homeostasis. To determine whether the apoD gene product was important for normal auditory function the hearing ability of an apoD knockout mouse was tested. The mouse was found to have a hearing threshold that was not significantly different to the control strain.

Animals↗

PubMed2004

Characterisation of DRASIC in the mouse inner ear.

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.

Acid Sensing Ion Channels↗

PubMed2002

In silico analyses of mouse inner-ear transcripts.

The development and function of the inner ear is complex requiring the correct and coordinated expression of many genes. The recent progress in the analyses of the human and other genomes has provided tools for identification of genes involved in hearing. As more and more nucleotide sequence information accumulates, experimental methods of molecular biology are rapidly being supplemented, and partially supplanted, by computational methods. In this study we present comprehensive in silico analyses of a cDNA library representing almost 1600 transcripts isolated from mouse inner ear. By mining the public databases we were able to rapidly and efficiently identify numerous transcripts likely to have a specific role in the auditory or vestibular function of the inner ear. Analyses revealed about 600 known genes and almost 100 inner-ear specific transcripts. Almost 50 of these are candidate genes for hearing impairment based on their chromosomal localization and inner-ear expression pattern. We describe a powerful approach to identify novel genes associated with hearing and vestibular function, further increasing our understanding of the molecular biology of the inner ear.

Animals↗