Tmc1

Summary

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
Species: mouse

Top Publications

  1. ncbi Beethoven, a mouse model for dominant, progressive hearing loss DFNA36
    Sarah Vreugde
    Department of Human Genetics and Molecular Medicine, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
    Nat Genet 30:257-8. 2002
  2. pmc Tmc1 is necessary for normal functional maturation and survival of inner and outer hair cells in the mouse cochlea
    Walter Marcotti
    School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9QG, UK
    J Physiol 574:677-98. 2006
  3. pmc Mechanotransduction in mouse inner ear hair cells requires transmembrane channel-like genes
    Yoshiyuki Kawashima
    Molecular Biology and Genetics Section, National Institute on Deafness and Other Communication Disorders, NIH, Rockville, Maryland 20850 3320, USA
    J Clin Invest 121:4796-809. 2011
  4. ncbi Characterization of the transmembrane channel-like (TMC) gene family: functional clues from hearing loss and epidermodysplasia verruciformis
    Kiyoto Kurima
    Section on Gene Structure and Function, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, 20850, Rockville, MD, USA
    Genomics 82:300-8. 2003
  5. pmc TMC1 and TMC2 are components of the mechanotransduction channel in hair cells of the mammalian inner ear
    Bifeng Pan
    Department of Otolaryngology, F M Kirby Neurobiology Center, Boston Children s Hospital, Harvard Medical School, 300 Longwood Avenue, Center for Life Sciences 12251, Boston, MA 02115, USA
    Neuron 79:504-15. 2013
  6. ncbi Dominant and recessive deafness caused by mutations of a novel gene, TMC1, required for cochlear hair-cell function
    Kiyoto Kurima
    Section on Gene Structure and Function, Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, 5 Research Court, Rockville, Maryland 20850, USA
    Nat Genet 30:277-84. 2002
  7. pmc The role of transmembrane channel-like proteins in the operation of hair cell mechanotransducer channels
    Kyunghee X Kim
    Department of Neuroscience, University of Wisconsin Medical School, Madison, WI 53706
    J Gen Physiol 142:493-505. 2013
  8. ncbi The nature of inherited deafness in deafness mice
    K P Steel
    Nature 288:159-61. 1980
  9. pmc The effects of Tmc1 Beethoven mutation on mechanotransducer channel function in cochlear hair cells
    Maryline Beurg
    Department of Neuroscience, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706
    J Gen Physiol 146:233-43. 2015
  10. pmc Development and localization of reverse-polarity mechanotransducer channels in cochlear hair cells
    Maryline Beurg
    Department of Neuroscience, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706
    Proc Natl Acad Sci U S A 113:6767-72. 2016

Scientific Experts

  • Sarah M McKay
  • Shehnaaz S M Manji
  • Sharon Oleskevich
  • Richardson N Leao
  • Gabor Keresztes
  • Carmen Martinez Cue
  • B J Keats
  • M Youssoufian
  • Maryline Beurg
  • Kiyoto Kurima
  • Andrew J Griffith
  • Robert Fettiplace
  • Bifeng Pan
  • Jeffrey R Holt
  • Yoshiyuki Kawashima
  • Bo Zhao
  • Kyunghee X Kim
  • Walter Marcotti
  • Tomoko Makishima
  • Yukako Asai
  • Valentina Labay
  • Corne J Kros
  • Laura F Corns
  • Adam C Goldring
  • Charles Askew
  • Wei Xiong
  • Ulrich Muller
  • Reo Maeda
  • Helmut Fuchs
  • Martin Hrabe de Angelis
  • Karen P Steel
  • Kiri Couchman
  • Stuart L Johnson
  • Natasha A Karp
  • Morag A Lewis
  • Shin ichiro Takayanagi
  • Yoshihiro Noguchi
  • Carmen Martínez-Cué
  • Alexandra Erven
  • Stacy S Drury
  • Anthony J Ricci
  • Seham Ebrahim
  • Yandan Yang
  • Prabuddha Sengupta
  • Kelly Monahan
  • Erin Child
  • Hiroshi Nakanishi
  • Bechara Kachar
  • Runjia Cui
  • Patrick Aebischer
  • Hena Ahmed
  • Bryan A Millis
  • Taro Fujikawa
  • Bernard L Schneider
  • Byung Yoon Choi
  • Cylia Rochat
  • Miloslav Sedlacek
  • Sarah Harkins-Perry
  • Rachel Clemens-Grisham
  • Teresa Nicolson
  • Edward R Wilcox
  • Thomas B Friedman
  • Peter G Barr-Gillespie
  • Linxuan Yan
  • Nicolas Grillet
  • Timothy Erickson
  • Hongyu Zhao
  • Clive P Morgan
  • Zizhen Wu
  • Katie S Kindt
  • Weike Mo
  • Sarah Vreugde
  • David N Furness
  • GWENAELLE S GELEOC
  • Geoffrey C Horwitz
  • Shanthini Mahendrasingam
  • Kotaro Ishikawa
  • Carole M Hackney
  • Andrea Lelli
  • Gwenaëlle S G Géléoc
  • Adam S Deardorff
  • Andrew Garrett
  • Bruce Walmsley
  • Doris K Wu
  • Charles C Della Santina
  • Frank Rattay
  • Robert Fyffe
  • Susanne Resatz
  • Lauren A Baker
  • Anna Karin B Gerdin

Detail Information

Publications46

  1. ncbi Beethoven, a mouse model for dominant, progressive hearing loss DFNA36
    Sarah Vreugde
    Department of Human Genetics and Molecular Medicine, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
    Nat Genet 30:257-8. 2002
    ..Here we describe the phenotype of the Beethoven (Bth) mouse mutant and a missense mutation in Tmc1 (transmembrane cochlear-expressed gene 1)...
  2. pmc Tmc1 is necessary for normal functional maturation and survival of inner and outer hair cells in the mouse cochlea
    Walter Marcotti
    School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9QG, UK
    J Physiol 574:677-98. 2006
    The 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 ..
  3. pmc Mechanotransduction in mouse inner ear hair cells requires transmembrane channel-like genes
    Yoshiyuki Kawashima
    Molecular Biology and Genetics Section, National Institute on Deafness and Other Communication Disorders, NIH, Rockville, Maryland 20850 3320, USA
    J Clin Invest 121:4796-809. 2011
    ..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 ..
  4. ncbi Characterization of the transmembrane channel-like (TMC) gene family: functional clues from hearing loss and epidermodysplasia verruciformis
    Kiyoto Kurima
    Section on Gene Structure and Function, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, 20850, Rockville, MD, USA
    Genomics 82:300-8. 2003
    Mutations of TMC1 cause deafness in humans and mice. TMC1 and a related gene, TMC2, are the founding members of a novel gene family...
  5. pmc TMC1 and TMC2 are components of the mechanotransduction channel in hair cells of the mammalian inner ear
    Bifeng Pan
    Department of Otolaryngology, F M Kirby Neurobiology Center, Boston Children s Hospital, Harvard Medical School, 300 Longwood Avenue, Center for Life Sciences 12251, Boston, MA 02115, USA
    Neuron 79:504-15. 2013
    ..To investigate the hypothesis that TMC1 and TMC2 proteins are components of the mechanosensitive ion channels that convert mechanical information into ..
  6. ncbi Dominant and recessive deafness caused by mutations of a novel gene, TMC1, required for cochlear hair-cell function
    Kiyoto Kurima
    Section on Gene Structure and Function, Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, 5 Research Court, Rockville, Maryland 20850, USA
    Nat Genet 30:277-84. 2002
    ..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...
  7. pmc The role of transmembrane channel-like proteins in the operation of hair cell mechanotransducer channels
    Kyunghee X Kim
    Department of Neuroscience, University of Wisconsin Medical School, Madison, WI 53706
    J Gen Physiol 142:493-505. 2013
    ..b>Tmc1 and Tmc2, two members of the transmembrane channel-like family, are necessary for mechanotransduction...
  8. ncbi The nature of inherited deafness in deafness mice
    K P Steel
    Nature 288:159-61. 1980
    ..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...
  9. pmc The effects of Tmc1 Beethoven mutation on mechanotransducer channel function in cochlear hair cells
    Maryline Beurg
    Department of Neuroscience, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706
    J Gen Physiol 146:233-43. 2015
    ..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-..
  10. pmc Development and localization of reverse-polarity mechanotransducer channels in cochlear hair cells
    Maryline Beurg
    Department of Neuroscience, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706
    Proc Natl Acad Sci U S A 113:6767-72. 2016
    ..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...
  11. ncbi Genetic marking of hematopoietic stem and endothelial cells: identification of the Tmtsp gene encoding a novel cell surface protein with the thrombospondin-1 domain
    Shin ichiro Takayanagi
    Laboratory of Stem Cell Therapy, Center for Experimental Medicine, University of Tokyo, Japan
    Blood 107:4317-25. 2006
    ....
  12. pmc Topology of transmembrane channel-like gene 1 protein
    Valentina Labay
    Molecular Biology and Genetics Section, Otolaryngology Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, Maryland 20850, USA
    Biochemistry 49:8592-8. 2010
    Mutations of transmembrane channel-like gene 1 (TMC1) cause hearing loss in humans and mice...
  13. pmc Lateral superior olive function in congenital deafness
    Kiri Couchman
    Division of Neuroscience, The John Curtin School of Medical Research, Australian National University, Canberra ACT, Australia
    Hear Res 277:163-75. 2011
    ..This could have clinical repercussions on the development of stimulation paradigms for spatial hearing with cochlear implants...
  14. pmc Tmc1 Point Mutation Affects Ca2+ Sensitivity and Block by Dihydrostreptomycin of the Mechanoelectrical Transducer Current of Mouse Outer Hair Cells
    Laura F Corns
    Department of Biomedical Science, University of Sheffield, Sheffield, South Yorkshire S10 2TN, United Kingdom
    J Neurosci 36:336-49. 2016
    ..Using Beethoven (Tmc1(Bth/Bth)) mice, which have an M412K point mutation in TMC1 that adds a positive charge, we found that Ca(2+..
  15. pmc Subunit determination of the conductance of hair-cell mechanotransducer channels
    Maryline Beurg
    Department of Neuroscience, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706 and
    Proc Natl Acad Sci U S A 112:1589-94. 2015
    ..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, ..
  16. pmc TMC1 and TMC2 Localize at the Site of Mechanotransduction in Mammalian Inner Ear Hair Cell Stereocilia
    Kiyoto Kurima
    Molecular Biology and Genetics Section, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, MD 20892, USA
    Cell Rep 12:1606-17. 2015
    ..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 ..
  17. doi Tmc gene therapy restores auditory function in deaf mice
    Charles Askew
    Department of Otolaryngology, F M Kirby Neurobiology Center, Boston Children s Hospital and Harvard Medical School, Boston, MA 02115, USA Neuroscience Graduate Program, University of Virginia, Charlottesville, VA 22908, USA
    Sci Transl Med 7:295ra108. 2015
    ..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...
  18. pmc Conductance and block of hair-cell mechanotransducer channels in transmembrane channel-like protein mutants
    Maryline Beurg
    Department of Neuroscience, University of Wisconsin Medical School, Madison, WI 53706
    J Gen Physiol 144:55-69. 2014
    Transmembrane 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...
  19. pmc Tip-link protein protocadherin 15 interacts with transmembrane channel-like proteins TMC1 and TMC2
    Reo Maeda
    Oregon Hearing Research Center and Vollum Institute, Oregon Health and Science University, Portland, OR 97239
    Proc Natl Acad Sci U S A 111:12907-12. 2014
    ..Tmc2a is an ortholog of mammalian TMC2, which along with TMC1 has been implicated in mechanotransduction in mammalian hair cells...
  20. pmc TMIE is an essential component of the mechanotransduction machinery of cochlear hair cells
    Bo Zhao
    Dorris Neuroscience Center, Department of Molecular and Cellular Neuroscience, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, CA 92037, USA
    Neuron 84:954-67. 2014
    ..The multisubunit composition of the transduction complex and the regulation of complex assembly by alternative splicing is likely critical for regulating channel properties in different hair cells and along the cochlea's tonotopic axis. ..
  21. doi Identification of three novel hearing loss mouse strains with mutations in the Tmc1 gene
    Shehnaaz S M Manji
    Genetic Hearing Research, Murdoch Childrens Research Institute, Royal Children s Hospital, Melbourne, Australia
    Am J Pathol 180:1560-9. 2012
    ..Similar to the previously reported Beethoven Tmc1 mutant, both p.Y182C and p.W554L are located outside a predicted transmembrane domain, whereas the p...
  22. ncbi Hyperpolarization-activated (I) currents in auditory brainstem neurons of normal and congenitally deaf mice
    Richardson N Leao
    Synapse and Hearing Laboratory, The John Curtin School of Medical Research, The Australian National University, PO Box 334, Canberra, ACT 0200, Australia
    Eur J Neurosci 22:147-57. 2005
    ..Our results provide further insight into the role of activity during development in regulating the membrane and firing properties of central neurons...
  23. pmc Optimising experimental design for high-throughput phenotyping in mice: a case study
    Natasha A Karp
    Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK
    Mamm Genome 21:467-76. 2010
    ..Consequently, in confirmatory studies, a power analysis along with the 3Rs can provide justification to increase the number of mice used...
  24. pmc An ENU-induced mutation of miR-96 associated with progressive hearing loss in mice
    Morag A Lewis
    Wellcome Trust Sanger Institute, Hinxton, UK
    Nat Genet 41:614-8. 2009
    ..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...
  25. ncbi The role of spontaneous activity in development of the endbulb of Held synapse
    Sarah M McKay
    Neuroscience Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW 2010, Australia
    Hear Res 230:53-63. 2007
    ..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...
  26. ncbi Altered sodium currents in auditory neurons of congenitally deaf mice
    Richardson N Leao
    Synapse and Hearing Laboratory, Division of Neuroscience, John Curtin School of Medical Research, Australian National University, PO Box 334, Canberra, ACT 0200, Australia
    Eur J Neurosci 24:1137-46. 2006
    ..Our results emphasize the importance of activity during development in regulating Na(+) channels...
  27. ncbi Genomics and hearing impairment
    B J Keats
    Department of Biometry and Genetics, Center for Molecular and Human Genetics, and Kresge Hearing Research Laboratory, Louisiana State University Medical Center, New Orleans 70112, USA
    Genome Res 9:7-16. 1999
    ..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...
  28. ncbi Distortion product otoacoustic emissions in hearing-impaired mutant mice
    K C Horner
    J Acoust Soc Am 78:1603-11. 1985
    ..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...
  29. ncbi Electrically-evoked responses in animals with progressive spiral ganglion degeneration
    K P Steel
    Hear Res 15:59-67. 1984
    ..These data may be relevant to the significant numbers of people with hereditary deafness among the hearing-impaired human population...
  30. ncbi Early degeneration of sensory and ganglion cells in the inner ear of mice with uncomplicated genetic deafness (dn): preliminary observations
    R Pujol
    Hear Res 12:57-63. 1983
    ....
  31. ncbi Preservation of central auditory function in the deafness mouse
    G R Bock
    Brain Res 239:608-12. 1982
    ....
  32. ncbi The deafness locus (dn) maps to mouse chromosome 19
    B J Keats
    Department of Biometry and Genetic, Kresge Hearing Research Laboratory, Louisiana State University Medical Center, New Orleans 70112
    Mamm Genome 6:8-10. 1995
    ..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...
  33. ncbi Mice heterozygous for the deafness gene have normal auditory thresholds
    J P Kirsch
    Department of Otolaryngology, Head and Neck Surgery, Tulane University Medical Center, New Orleans, Louisiana
    Hear Res 67:51-4. 1993
    ..A 'generational backtracking' method was used to increase the probability of identifying homozygous (+/+) animals of the curly-tail strain...
  34. ncbi Expression of the winged helix genes fkh-4 and fkh-5 defines domains in the central nervous system
    K H Kaestner
    Division of Molecular Biology of the Cell I, German Cancer Research Centre, Heidelberg, Germany
    Mech Dev 55:221-30. 1996
    ..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...
  35. ncbi The mouse deafness locus (dn) is associated with an inversion on chromosome 19
    A M Viñas
    Department of Biochemistry and Molecular Biology, Louisiana State University Medical Center, New Orleans 70112, USA
    Biochim Biophys Acta 1407:257-62. 1998
    ..The dn gene is probably the orthologue of the human DFNB7/DFNB11 gene on chromosome 9...
  36. ncbi 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
    D A Scott
    Department of Pediatrics, University of Iowa Hospitals and Clinics, Iowa City, IA 52242 1078, USA
    Gene 215:461-9. 1998
    ..These data Suggest that the ZNF216 gene is unlikely to be responsible for hearing loss at the DFNB7/11 and dn loci...
  37. pmc Multiple quantitative trait loci modify cochlear hair cell degeneration in the Beethoven (Tmc1Bth) mouse model of progressive hearing loss DFNA36
    Yoshihiro Noguchi
    Section on Gene Structure and Function, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, MD 20850 3320, USA
    Genetics 173:2111-9. 2006
    ..mutations of transmembrane channel-like gene 1 (TMC1) cause progressive sensorineural hearing loss in humans and Beethoven (Tmc1Bth/+) mice...
  38. pmc Synaptic transmission in the auditory brainstem of normal and congenitally deaf mice
    Sharon Oleskevich
    Division of Neuroscience, The John Curtin School of Medical Research, The Australian National University, Canberra, ACT 0200, Australia
    J Physiol 540:447-55. 2002
    ....
  39. pmc TMC and EVER genes belong to a larger novel family, the TMC gene family encoding transmembrane proteins
    Gabor Keresztes
    Department of Otolaryngology and Program in Neuroscience, Harvard Medical School, Boston, MA, USA
    BMC Genomics 4:24. 2003
    Mutations in the transmembrane cochlear expressed gene 1 (TMC1) cause deafness in human and mouse...
  40. ncbi Mouse tales from Kresge: the deafness mouse
    Stacy S Drury
    Department of Genetics, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, USA
    J Am Acad Audiol 14:296-301. 2003
    ..A mutation in Tmc1 is also found in Beethoven (Bth), which is another deaf mouse mutant...
  41. pmc Reduced low-voltage activated K+ conductances and enhanced central excitability in a congenitally deaf (dn/dn) mouse
    Richardson N Leao
    Synapse and Hearing Laboratory, Division of Neuroscience, John Curtin School of Medical Research, Australian National University, PO Box 334, Canberra, ACT 0200, Australia
    J Physiol 559:25-33. 2004
    ....
  42. pmc Presynaptic plasticity at two giant auditory synapses in normal and deaf mice
    S Oleskevich
    Garvan Institute of Medical Research, St Vincents Hospital, 384 Victoria Street, Sydney, NSW 2010, Australia
    J Physiol 560:709-19. 2004
    ..Synaptic transmission at the calyx synapse is more powerful and has less capacity for developmental plasticity compared to the endbulb synapse...
  43. ncbi Behavioral, cognitive and biochemical responses to different environmental conditions in male Ts65Dn mice, a model of Down syndrome
    Carmen Martínez-Cué
    Laboratory of Developmental Neurobiology, Department of Physiology and Pharmacology, Faculty of Medicine, University of Cantabria, Santander, Spain
    Behav Brain Res 163:174-85. 2005
    ..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...
  44. ncbi Development of a robust central auditory synapse in congenital deafness
    M Youssoufian
    Division of Neuroscience, John Curtin School of Medical Research, Australian National University, PO Box 334, Canberra ACT 2600, Australia
    J Neurophysiol 94:3168-80. 2005
    ..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...
  45. ncbi Degeneration followed by partial regeneration of the organ of Corti in deafness (dn/dn) mice
    D B Webster
    Kresge Hearing Research Laboratory, Department of Otorhinolaryngology, Louisiana State University Medical Center, New Orleans 70112
    Exp Neurol 115:27-31. 1992
    ..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...