Genomes and Genes
Gene Symbol: Tmc1
Description: transmembrane channel-like gene family 1
Alias: 4933416G09Rik, Beethoven, Bth, CWEA1, transmembrane channel-like protein 1, deafness protein, transmembrane cochlear-expressed protein 1, transmembrane, cochlear expressed 1
- Pan B, GELEOC G, Asai Y, Horwitz G, Kurima K, Ishikawa K, et al. TMC1 and TMC2 are components of the mechanotransduction channel in hair cells of the mammalian inner ear. Neuron. 2013;79:504-15 pubmed publisher..To investigate the hypothesis that TMC1 and TMC2 proteins are components of the mechanosensitive ion channels that convert mechanical information into ..
- Kurima K, Peters L, Yang Y, Riazuddin S, Ahmed Z, Naz S, et al. Dominant and recessive deafness caused by mutations of a novel gene, TMC1, required for cochlear hair-cell function. Nat Genet. 2002;30:277-84 pubmed..We identified eight mutations in a new gene, transmembrane cochlear-expressed gene 1 (TMC1), in a DFNA36 family and eleven DFNB7/B11 families. We detected a 1...
- Marcotti W, Erven A, Johnson S, Steel K, Kros C. Tmc1 is necessary for normal functional maturation and survival of inner and outer hair cells in the mouse cochlea. J Physiol. 2006;574:677-98 pubmedThe deafness (dn) and Beethoven (Bth) mutant mice are models for profound congenital deafness (DFNB7/B11) and progressive hearing loss (DFNA36), respectively, caused by recessive and dominant mutations of transmembrane cochlear-expressed ..
- Kim K, Beurg M, Hackney C, Furness D, Mahendrasingam S, Fettiplace R. The role of transmembrane channel-like proteins in the operation of hair cell mechanotransducer channels. J Gen Physiol. 2013;142:493-505 pubmed publisher..b>Tmc1 and Tmc2, two members of the transmembrane channel-like family, are necessary for mechanotransduction...
- Kurima K, Yang Y, Sorber K, Griffith A. Characterization of the transmembrane channel-like (TMC) gene family: functional clues from hearing loss and epidermodysplasia verruciformis. Genomics. 2003;82:300-8 pubmedMutations of TMC1 cause deafness in humans and mice. TMC1 and a related gene, TMC2, are the founding members of a novel gene family...
- Vreugde S, Erven A, Kros C, Marcotti W, Fuchs H, Kurima K, et al. Beethoven, a mouse model for dominant, progressive hearing loss DFNA36. Nat Genet. 2002;30:257-8 pubmed..Here we describe the phenotype of the Beethoven (Bth) mouse mutant and a missense mutation in Tmc1 (transmembrane cochlear-expressed gene 1)...
- Kawashima Y, Géléoc G, Kurima K, Labay V, Lelli A, Asai Y, et al. Mechanotransduction in mouse inner ear hair cells requires transmembrane channel-like genes. J Clin Invest. 2011;121:4796-809 pubmed publisher..the identity of these ion channels is unknown, and mutations in the gene encoding transmembrane channel-like 1 (TMC1) cause hearing loss without vestibular dysfunction in both mice and humans, we investigated the contribution of ..
- Steel K, Bock G. The nature of inherited deafness in deafness mice. Nature. 1980;288:159-61 pubmed..Our data indicate that stimulus-related cochlear potentials do not develop even though hair cells are present in the young animal. The endocochlear potential is present in the scala media, but behaves abnormally during anoxia. ..
- Wu Z, Grillet N, Zhao B, Cunningham C, Harkins Perry S, Coste B, et al. Mechanosensory hair cells express two molecularly distinct mechanotransduction channels. Nat Neurosci. 2017;20:24-33 pubmed publisher..show that its activity is affected by mutations in the genes encoding the transmembrane proteins TMHS, TMIE, TMC1 and TMC2...
- Beurg M, Xiong W, Zhao B, Muller U, Fettiplace R. Subunit determination of the conductance of hair-cell mechanotransducer channels. Proc Natl Acad Sci U S A. 2015;112:1589-94 pubmed publisher..Two such proteins are transmembrane channel-like protein isoform 1 (TMC1) and tetraspan membrane protein of hair cell stereocilia (TMHS, also known as lipoma HMGIC fusion partner-like 5, ..
- Askew C, Rochat C, Pan B, Asai Y, Ahmed H, Child E, et al. Tmc gene therapy restores auditory function in deaf mice. Sci Transl Med. 2015;7:295ra108 pubmed publisher..Mice that carry targeted deletion of Tmc1 or a dominant Tmc1 point mutation, known as Beethoven, are good models for human DFNB7/11 and DFNA36...
- Steel K, Bock G. Electrically-evoked responses in animals with progressive spiral ganglion degeneration. Hear Res. 1984;15:59-67 pubmed..These data may be relevant to the significant numbers of people with hereditary deafness among the hearing-impaired human population. ..
- Viñas A, Drury S, DeAngelis M, Den Z, Huang J, Berlin C, et al. The mouse deafness locus (dn) is associated with an inversion on chromosome 19. Biochim Biophys Acta. 1998;1407:257-62 pubmed..The dn gene is probably the orthologue of the human DFNB7/DFNB11 gene on chromosome 9. ..
- Keats B, Nouri N, Huang J, Money M, Webster D, Berlin C. The deafness locus (dn) maps to mouse chromosome 19. Mamm Genome. 1995;6:8-10 pubmed..The identification of the defective gene in the mouse will help to explain the mechanism that causes hair cell degeneration and is likely to identify a homologous gene for deafness in humans. ..
- Maeda R, Kindt K, Mo W, Morgan C, Erickson T, Zhao H, et al. Tip-link protein protocadherin 15 interacts with transmembrane channel-like proteins TMC1 and TMC2. Proc Natl Acad Sci U S A. 2014;111:12907-12 pubmed publisher..Tmc2a is an ortholog of mammalian TMC2, which along with TMC1 has been implicated in mechanotransduction in mammalian hair cells...
- Pujol R, Shnerson A, Lenoir M, Deol M. Early degeneration of sensory and ganglion cells in the inner ear of mice with uncomplicated genetic deafness (dn): preliminary observations. Hear Res. 1983;12:57-63 pubmed
- Erickson T, Morgan C, Olt J, Hardy K, Busch Nentwich E, Maeda R, et al. Integration of Tmc1/2 into the mechanotransduction complex in zebrafish hair cells is regulated by Transmembrane O-methyltransferase (Tomt). elife. 2017;6: pubmed publisher..We found that Tmc1/2 proteins are specifically excluded from the hair bundle in tomt mutants, whereas other MET complex ..
- Takayanagi S, Hiroyama T, Yamazaki S, Nakajima T, Morita Y, Usui J, et al. Genetic marking of hematopoietic stem and endothelial cells: identification of the Tmtsp gene encoding a novel cell surface protein with the thrombospondin-1 domain. Blood. 2006;107:4317-25 pubmed
- Kaestner K, Schutz G, Monaghan A. Expression of the winged helix genes fkh-4 and fkh-5 defines domains in the central nervous system. Mech Dev. 1996;55:221-30 pubmed..5 centiMorgans (cM) and fkh-4 to chromosome 19 at 10.5 cM. The potential relationship of the two genes to the mouse mutations staggerer and small thymus (for fkh-5) and muscle deficient (for fkh-4) is discussed. ..
- Kirsch J, Money M, Webster D. Mice heterozygous for the deafness gene have normal auditory thresholds. Hear Res. 1993;67:51-4 pubmed..A 'generational backtracking' method was used to increase the probability of identifying homozygous (+/+) animals of the curly-tail strain. ..
- Scott D, Greinwald J, Marietta J, Drury S, Swiderski R, Vinas A, et al. Identification and mutation analysis of a cochlear-expressed, zinc finger protein gene at the DFNB7/11 and dn hearing-loss loci on human chromosome 9q and mouse chromosome 19. Gene. 1998;215:461-9 pubmed..These data Suggest that the ZNF216 gene is unlikely to be responsible for hearing loss at the DFNB7/11 and dn loci. ..
- Kurima K, Ebrahim S, Pan B, Sedlacek M, Sengupta P, Millis B, et al. TMC1 and TMC2 Localize at the Site of Mechanotransduction in Mammalian Inner Ear Hair Cell Stereocilia. Cell Rep. 2015;12:1606-17 pubmed publisher..Transmembrane channel-like 1 and 2 (TMC1 and TMC2) are essential for MET and are hypothesized to be components of the MET complex, but evidence for their ..
- Couchman K, Garrett A, Deardorff A, Rattay F, Resatz S, Fyffe R, et al. Lateral superior olive function in congenital deafness. Hear Res. 2011;277:163-75 pubmed publisher..This could have clinical repercussions on the development of stimulation paradigms for spatial hearing with cochlear implants. ..
- Drury S, Keats B. Mouse tales from Kresge: the deafness mouse. J Am Acad Audiol. 2003;14:296-301 pubmed..A mutation in Tmc1 is also found in Beethoven (Bth), which is another deaf mouse mutant...
- Beurg M, Goldring A, Fettiplace R. The effects of Tmc1 Beethoven mutation on mechanotransducer channel function in cochlear hair cells. J Gen Physiol. 2015;146:233-43 pubmed publisher..We found that in outer hair cells of Beethoven mice containing a M412K point mutation in TMC1, MT channels had a similar unitary conductance to that of wild-..
- Cunningham C, Wu Z, Jafari A, Zhao B, Schrode K, Harkins Perry S, et al. The murine catecholamine methyltransferase mTOMT is essential for mechanotransduction by cochlear hair cells. elife. 2017;6: pubmed publisher..Defects in this process are likely mechanistically linked to deafness caused by mutations in LRTOMT/Tomt. ..
- Labay V, Weichert R, Makishima T, Griffith A. Topology of transmembrane channel-like gene 1 protein. Biochemistry. 2010;49:8592-8 pubmed publisherMutations of transmembrane channel-like gene 1 (TMC1) cause hearing loss in humans and mice...
- Beurg M, Goldring A, Ricci A, Fettiplace R. Development and localization of reverse-polarity mechanotransducer channels in cochlear hair cells. Proc Natl Acad Sci U S A. 2016;113:6767-72 pubmed publisher..in cochlear hair cells after tip-link destruction with BAPTA, in transmembrane channel-like protein isoforms 1/2 (Tmc1:Tmc2) double mutants, and during perinatal development...
- Giese A, Tang Y, Sinha G, Bowl M, Goldring A, Parker A, et al. CIB2 interacts with TMC1 and TMC2 and is essential for mechanotransduction in auditory hair cells. Nat Commun. 2017;8:43 pubmed publisher..that calcium and integrin-binding protein 2 binds to the components of the hair cell mechanotransduction complex, TMC1 and TMC2, and these interactions are disrupted by deafness-causing Cib2 mutations...
- Webster D. Degeneration followed by partial regeneration of the organ of Corti in deafness (dn/dn) mice. Exp Neurol. 1992;115:27-31 pubmed..A tunnel of Corti and space of Nuel are also present in the apex but there are no hair cells. Mechanisms are not known for either the degeneration or the regeneration. ..
- McKay S, Oleskevich S. The role of spontaneous activity in development of the endbulb of Held synapse. Hear Res. 2007;230:53-63 pubmed..7-fold) after hearing onset while release probability remained constant (0.5). Overall, the results in deafness mice suggest that synaptic strength is altered in the absence of spontaneous auditory nerve activity...
- Leao R, Svahn K, Berntson A, Walmsley B. Hyperpolarization-activated (I) currents in auditory brainstem neurons of normal and congenitally deaf mice. Eur J Neurosci. 2005;22:147-57 pubmed..Our results provide further insight into the role of activity during development in regulating the membrane and firing properties of central neurons. ..
- Karp N, Baker L, Gerdin A, Adams N, Ramirez Solis R, White J. Optimising experimental design for high-throughput phenotyping in mice: a case study. Mamm Genome. 2010;21:467-76 pubmed publisher..Consequently, in confirmatory studies, a power analysis along with the 3Rs can provide justification to increase the number of mice used. ..
- Leao R, Naves M, Leao K, Walmsley B. Altered sodium currents in auditory neurons of congenitally deaf mice. Eur J Neurosci. 2006;24:1137-46 pubmed..Our results emphasize the importance of activity during development in regulating Na(+) channels. ..
- Keats B, Berlin C. Genomics and hearing impairment. Genome Res. 1999;9:7-16 pubmed..The availability of high-resolution maps of the human and mouse genomes and new technologies for gene identification are advancing molecular understanding of hearing impairment and the complex mechanisms of the auditory system. ..
- Keresztes G, Mutai H, Heller S. TMC and EVER genes belong to a larger novel family, the TMC gene family encoding transmembrane proteins. BMC Genomics. 2003;4:24 pubmed publisherMutations in the transmembrane cochlear expressed gene 1 (TMC1) cause deafness in human and mouse...
- Manji S, Miller K, Williams L, Dahl H. Identification of three novel hearing loss mouse strains with mutations in the Tmc1 gene. Am J Pathol. 2012;180:1560-9 pubmed publisher..Similar to the previously reported Beethoven Tmc1 mutant, both p.Y182C and p.W554L are located outside a predicted transmembrane domain, whereas the p...
- Beurg M, Kim K, Fettiplace R. Conductance and block of hair-cell mechanotransducer channels in transmembrane channel-like protein mutants. J Gen Physiol. 2014;144:55-69 pubmed publisherTransmembrane channel-like (TMC) proteins TMC1 and TMC2 are crucial to the function of the mechanotransducer (MT) channel of inner ear hair cells, but their precise function has been controversial...
- Youssoufian M, Oleskevich S, Walmsley B. Development of a robust central auditory synapse in congenital deafness. J Neurophysiol. 2005;94:3168-80 pubmed..These results demonstrate that early development at this robust synapse proceeds normally with congenital deafness, suggesting that auditory nerve activity does not affect the development of synaptic strength at the calyx of Held. ..
- Oleskevich S, Youssoufian M, Walmsley B. Presynaptic plasticity at two giant auditory synapses in normal and deaf mice. J Physiol. 2004;560:709-19 pubmed..Synaptic transmission at the calyx synapse is more powerful and has less capacity for developmental plasticity compared to the endbulb synapse. ..
- Horner K, Lenoir M, Bock G. Distortion product otoacoustic emissions in hearing-impaired mutant mice. J Acoust Soc Am. 1985;78:1603-11 pubmed..DP's of small amplitude were recorded but the thresholds were raised by about 30 dB. The data suggest that the 2f1-f2 emission can be used as a noninvasive monitor of cochlear function. ..
- Kocher W. [Studies on the genetics and pathology of the development of 8 labyrinth mutants (deaf-waltzer-shaker mutants) in the mouse (Mus musculus)]. Z Vererbungsl. 1960;91:114-40 pubmed
- Corns L, Johnson S, Kros C, Marcotti W. Tmc1 Point Mutation Affects Ca2+ Sensitivity and Block by Dihydrostreptomycin of the Mechanoelectrical Transducer Current of Mouse Outer Hair Cells. J Neurosci. 2016;36:336-49 pubmed publisher..Using Beethoven (Tmc1(Bth/Bth)) mice, which have an M412K point mutation in TMC1 that adds a positive charge, we found that Ca(2+..
- Martinez Cue C, Rueda N, Garcia E, Davisson M, Schmidt C, Flórez J. Behavioral, cognitive and biochemical responses to different environmental conditions in male Ts65Dn mice, a model of Down syndrome. Behav Brain Res. 2005;163:174-85 pubmed..It is suggested that an excess of social and/or physical stimulation in Ts65Dn mice may affect cognition by disturbing the emotional and behavioral components of the learning process. ..
- Oleskevich S, Walmsley B. Synaptic transmission in the auditory brainstem of normal and congenitally deaf mice. J Physiol. 2002;540:447-55 pubmed
- Noguchi Y, Kurima K, Makishima T, de Angelis M, Fuchs H, Frolenkov G, et al. Multiple quantitative trait loci modify cochlear hair cell degeneration in the Beethoven (Tmc1Bth) mouse model of progressive hearing loss DFNA36. Genetics. 2006;173:2111-9 pubmed..mutations of transmembrane channel-like gene 1 (TMC1) cause progressive sensorineural hearing loss in humans and Beethoven (Tmc1Bth/+) mice...
- Lewis M, Quint E, Glazier A, Fuchs H, de Angelis M, Langford C, et al. An ENU-induced mutation of miR-96 associated with progressive hearing loss in mice. Nat Genet. 2009;41:614-8 pubmed publisher..This is the first microRNA found associated with deafness, and diminuendo represents a model for understanding and potentially moderating progressive hair cell degeneration in hearing loss more generally. ..
- Leao R, Berntson A, Forsythe I, Walmsley B. Reduced low-voltage activated K+ conductances and enhanced central excitability in a congenitally deaf (dn/dn) mouse. J Physiol. 2004;559:25-33 pubmed
- Bock G, Frank M, Steel K. Preservation of central auditory function in the deafness mouse. Brain Res. 1982;239:608-12 pubmed