A new gene for deafness in the mouse

Deol, M. S.; Kocher, Walter

doi:10.1038/hdy.1958.46

Cited by 76 publications

(35 citation statements)

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“…In three families from Tamil Nadu in India showing recessive deafness, the defective gene was mapped to 9q13-q21, defining a new deafness locus (DFNB7/DFNB11) (Jain et al, 1995). The syntenic region in mouse also harbors a locus responsible for recessive deafness in the dn mouse (Deol and Kocher, 1958). showed in multiple families that the DFNB7/ DFNB11 gene, as well as those for the dominant human deafness DFNA36 and the dn mouse, encode a novel protein they called TMC1 (transmembrane cochlear-expressed gene 1, renamed transmembrane channel-like 1).…”

Section: Challenges For Molecular Identificationmentioning

confidence: 99%

Are TMCs the Mechanotransduction Channels of Vertebrate Hair Cells?

Corey

Holt

2016

J. Neurosci.

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Sensory transduction in vertebrate hair cells and the molecules that mediate it have long been of great interest. Some components of the mechanotransduction apparatus have been identified, most as deafness gene products. Although prior candidates for the mechanotransduction channel have been proposed, each has faded with new evidence. Now, two strong candidates, TMC1 and TMC2 (transmembrane channel-like), have emerged from discovery of deafness genes in humans and mice. They are expressed at the right time during development: exactly at the onset of mechanosensitivity. They are expressed in the right place: in hair cells but not surrounding cells. Fluorescently tagged TMCs localize to the tips of stereocilia, the site of the transduction channels. TMCs bind other proteins essential for mechanosensation, suggesting a larger transduction complex. Although TMC1 and TMC2 can substitute for each other, genetic deletion of both renders mouse hair cells mechanically insensitive. Finally, the conductance and Ca 2ϩ selectivity of the transduction channels depend on the TMC proteins, differing when hair cells express one or the other TMC, and differing if TMC1 harbors a point mutation. Some contrary evidence has emerged: a current activated in hair cells by negative pressure, with some similarity to the transduction current, persists in TMC knock-outs. But it is not clear that this anomalous current is carried by the same proteins. Further evidence is desired, such as production of a mechanically gated conductance by pure TMCs. But the great majority of evidence is consistent with these TMCs as pore-forming subunits of the long-sought hair-cell transduction channel.

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Section: Challenges For Molecular Identificationmentioning

confidence: 99%

Are TMCs the Mechanotransduction Channels of Vertebrate Hair Cells?

Corey

Holt

2016

J. Neurosci.

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“…To our knowledge, only two mouse mutations, deafness (dn) (Keats et al, 1995) and deaf (V df ) (Deol, 1956), have been reported that are not associated with balance or with other non-auditory defects. In contrast to the congenital, syndromic deafness caused by most mouse mutations, certain inbred strains of mice exhibit a progressive, non-syndromic hearing loss, with onset at more advanced ages.…”

Section: Introductionmentioning

confidence: 99%

Assessment of hearing in 80 inbred strains of mice by ABR threshold analyses

1999

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The common occurrence of hearing loss in both humans and mice, and the anatomical and functional similarities of their inner ears, attest to the potential of mice being used as models to study inherited hearing loss. A large-scale, auditory screening project is being undertaken at The Jackson Laboratory (TJL) to identify mice with inherited hearing disorders. To assess hearing sensitivity, at least five mice from each inbred strain had auditory brainstem response (ABR) thresholds determined. Thus far, we have screened 80 inbred strains of mice; 60 of them exhibited homogeneous ABR threshold values not significantly different from those of the control strain CBA/CaJ. This large database establishes a reliable reference for normal hearing mouse strains. The following 16 inbred strains exhibited significantly elevated ABR thresholds before the age of 3 months: 129/J, 129/ReJ, 129/ SvJ, A/J, ALR/LtJ, ALS/LtJ, BUB/BnJ, C57BLKS/J, C57BR/cdJ, C57L/J, DBA/2J, I/LnJ, MA/MyJ, NOD/LtJ, NOR/LtJ, and SKH2/J. These hearing impaired strains may serve as models for some forms of human non-syndromic hearing loss and aid in the identification of the underlying genes.

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“…They were provided by J, Goyens and E. Noirot, the latter having transferred the dn gene from litters of Deol's strain to a stock originating from the colony of outbrcd albino mice which she has described and has been maintaining since her first report (Noirot, 1964;Goyens & Noirot, 1974). Deol and Kocher (1958) have described the sequence of histopalhological changes in the ears of the homozygous (dnidn) animals. At birth, their inner ear structures appear normal.…”

Section: Methodsmentioning

confidence: 99%

“…Mutant mice earring the deafness (dn) gene described by Deol (1956) were used for this study. They were provided by J, Goyens and E. Noirot, the latter having transferred the dn gene from litters of Deol's strain to a stock originating from the colony of outbrcd albino mice which she has described and has been maintaining since her first report (Noirot, 1964;Goyens & Noirot, 1974).…”

Section: Methodsmentioning

confidence: 99%

Consequences of Auditory Deprivation in Animals and Humans

Périer¹,

Alegría²,

Buyse³

et al. 1984

Acta Oto-Laryngologica

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An electron microscopic study of the cerebral cortex of mutant deaf mice (Deol's dn gene) has shown differences in synaptic organisation between these mice and normally hearing ones. In the auditory cortex of the deaf mice, there are fewer synapses and these are larger than in the normally hearing, whereas there is no difference between these two categories in the visual cortex. These results are the reverse of those observed by other authors in the occipital cortex of rats raised in an enriched or impoverished environment. In humans, the functional consequences of early hearing loss have been investigated on moderately to severely deaf (60-80 db mean loss) youngsters, who have been tested for their capacity of categorical perception, auditory discrimination, and production of significant contrasts between stop consonants. Categorical perception was absent in alt but one subject. Auditory discrimination was poor for both the voiced-voiceless contrast and the place of articulation contrast. In the production experiments, the subjects had greater difficulty in producing the voiced-voiceless than the place of articulation contrasts. The possible relevance of these animal and human studies to cochlear implantation is discussed. I. ANIMAL STUDIESAuditory deprivation in animals can be obtained either by destruction of the inner ear or by restriction of auditory input.Ear destruction has been done by Levi-Montalcini (1949) and Powell & Erulkar (1961). It results in transsynaptic atrophy of the brainstem and thalamic auditory nuclei, this atrophy consisting of a reduction in size of the neurons without actual neuronal destruction, a lesion which might be reversible if proper stimulation could be restored.Complete suppression of auditory input to the intact animal cannot be achieved, because of bone conduction perception of the animal's own inner noises, so that only the results of auditory restriction are available (Wolf, 1943;Gauron & Becker, 1959). New-born rats submitted to such a restriction for several weeks or months have no difficulty in learning frequency discrimination but are less proficient than controls for discrimination of temporal sequences (Tees, 1967), and their hearing thresholds measured by electric response audiometry are elevated (Batkin et al., 1970). Webster & Webster (1977-79) observed that both postnatal auditory deprivation and experimentally produced conductive hearing loss in mice result in incomplete maturation of most brainstem auditory neurons. There is a critical period, before 45 days of age, during which acoustic stimulation has a more pronounced effect on neuronal maturation than the same stimulation given between 45 and 90 days. The changes observed were only partially reversible in animals which were submitted to auditory deprivation until 45 days of age and then placed in a normal acoustic environment. Bock et al. (1982), studying Deol's strain of deafness (dn) mutant mice, have recorded evoked potentials of normal or higher than normal amplitude at the level of the inferior colli...

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A new gene for deafness in the mouse

Cited by 76 publications

References 1 publication

Are TMCs the Mechanotransduction Channels of Vertebrate Hair Cells?

Are TMCs the Mechanotransduction Channels of Vertebrate Hair Cells?

Assessment of hearing in 80 inbred strains of mice by ABR threshold analyses

Consequences of Auditory Deprivation in Animals and Humans

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