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Over-expression of myosin7A in cochlear hair cells of circling mice

Abstract

Circling mouse (C57BL/6J-cir/cir) deleted the transmembrane inner ear (Tmie) gene is an animal model for human non-syndromic recessive deafness, DFNB6. In circling mouse, hair cells in the cochlea have degenerated and hair bundles have become irregularity as time goes on. Tmie protein carries out a function of the mechanoelectrical transduction channel in cochlear hair cells. Myosin7a (MYO7A) protein has key roles in development of the cochlear hair bundles as well as in the function of cochlear hair cells. To find whether Tmie protein interacts with MYO7A proteins in the cochlea postnatal developmental stage, we investigated expression of the MYO7A proteins in the cochlear hair cells of circling mice by western blot analysis and whole mount immunofluorescence at postnatal day 5 (P5). The expression of MYO7A showed statistically significant increase in the cochlea of C57BL/6J-+/cir and C57BL/6J-cir/cir mice than that of C57BL/6J-+/+ mice. The MYO7A intensity of the cochlear hair cells also increased in C57BL/6J-+/cir and C57BL/6J-cir/cir mice compared with those of C57BL/6J-+/+ mice. Taken together, the results indicate that Tmie protein may have an important role with MYO7A protein in the development and maintenance of the stereociliary bundles during postnatal developmental stage of the cochlea.

References

  1. Schrijver I. Hereditary non-syndromic sensorineural hearing loss: transforming silence to sound. J Mol Diagn 2004; 6(4): 275–284.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  2. Mason JA, Herrmann KR. Universal infant hearing screening by automated auditory brainstem response measurement. Pediatrics 1998; 101(2): 221–228.

    CAS  PubMed  Article  Google Scholar 

  3. Parving A. The need for universal neonatal hearing screening-some aspects of epidemiology and identification. Acta Paediatr Suppl 1999; 88(432): 69–72.

    CAS  PubMed  Article  Google Scholar 

  4. Stelma F, Bhutta MF. Non-syndromic hereditary sensorineural hearing loss: review of the genes involved. J Laryngol Otol 2014; 128(1): 13–21.

    CAS  PubMed  Article  Google Scholar 

  5. Van Camp G, Willems PJ, Smith RJ. Nonsyndromic hearing impairment: unparalleled heterogeneity. Am J Hum Genet 1997; 60(4): 758–764.

    PubMed  PubMed Central  Google Scholar 

  6. ACMG (American College of Medical Genetics). Genetics Evaluation Guidelines for the Etiologic Diagnosis of Congenital Hearing Loss. Genetic Evaluation of Congenital Hearing Loss Expert Panel. ACMG statement. Genet Med 2002; 4(3): 162–171.

    Google Scholar 

  7. Hone SW, Smith RJ. Medical evaluation of pediatric hearing loss. Laboratory, radiographic, and genetic testing. Otolaryngol Clin North Am 2002; 35(4): 751–764.

    PubMed  Article  Google Scholar 

  8. Lee JW, Ryoo ZY, Lee EJ, Hong SH, Chung WH, Lee HT, Chung KS, Kim TY, Oh YS, Suh JG. Circling mouse, a spontaneous mutant in the inner ear. Exp Anim 2002; 51(2): 167–171.

    CAS  PubMed  Article  Google Scholar 

  9. Cho KI, Suh JG, Lee JW, Hong SH, Kang TC, Oh YS, Ryoo ZY. The circling mouse (C57BL/6J-cir) has a 40-kilobase genomic deletion that includes the transmembrane inner ear (tmie) gene. Comp Med 2006; 56(6): 476–481.

    CAS  PubMed  Google Scholar 

  10. Chung WH, Kim KR, Cho YS, Cho DY, Woo JH, Ryoo ZY, Cho KI, Hong SH. Cochlear pathology of the circling mouse: a new mouse model of DFNB6. Acta Otolaryngol 2007; 127(3): 244–251.

    CAS  PubMed  Article  Google Scholar 

  11. Zhao B, Wu Z, Grillet N, Yan L, Xiong W, Harkins-Perry S, Müller U. TMIE is an essential component of the mechanotransduction machinery of cochlear hair cells. Neuron 2014; 84(5): 954–967.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  12. Grati M, Kachar B. Myosin VIIa and sans localization at stereocilia upper tip-link density implicates these Usher syndrome proteins in mechanotransduction. Proc Natl Acad Sci USA 2011; 108(28): 11476–11481.

    CAS  PubMed  Article  Google Scholar 

  13. Maniak M. Cell adhesion: ushering in a new understanding of myosin VII. Curr Biol 2001; 11(8): R315–R317.

    CAS  PubMed  Article  Google Scholar 

  14. Hasson T, Heintzelman MB, Santos-Sacchi J, Corey DP, Mooseker MS. Expression in cochlea and retina of myosin VIIa, the gene product defective in Usher syndrome type 1B. Proc Natl Acad Sci USA 1995; 92(21): 9815–9819.

    CAS  PubMed  Article  Google Scholar 

  15. Hasson T, Gillespie PG, Garcia JA, MacDonald RB, Zhao Y, Yee AG, Mooseker MS, Corey DP. Unconventional myosins in innerear sensory epithelia. J Cell Biol 1997; 137(6): 1287–1307.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  16. Lefèvre G, Michel V, Weil D, Lepelletier L, Bizard E, Wolfrum U, Hardelin JP, Petit C. A core cochlear phenotype in USH1 mouse mutants implicates fibrous links of the hair bundle in its cohesion, orientation and differential growth. Development 2008; 135(8): 1427–1437.

    PubMed  Article  Google Scholar 

  17. Self T, Mahony M, Fleming J, Walsh J, Brown SD, Steel KP. Shaker-1 mutations reveal roles for myosin VIIA in both development and function of cochlear hair cells. Development 1998; 125(4): 557–566.

    CAS  PubMed  Google Scholar 

  18. Kros CJ, Marcotti W, van Netten SM, Self TJ, Libby RT, Brown SD, Richardson GP, Steel KP. Reduced climbing and increased slipping adaptation in cochlear hair cells of mice with Myo7a mutations. Nat Neurosci 2002; 5(1): 41–47.

    CAS  PubMed  Article  Google Scholar 

  19. Cho KI, Lee JW, Kim KS, Lee EJ, Suh JG, Lee HJ, Kim HT, Hong SH, Chung WH, Chang KT, Hyun BH, Oh YS, Ryoo ZY. Fine mapping of the circling (cir) gene on the distal portion of mouse chromosome 9. Comp Med 2003; 53(6): 642–648.

    CAS  PubMed  Google Scholar 

  20. Mitchem KL, Hibbard E, Beyer LA, Bosom K, Dootz GA, Dolan DF, Johnson KR, Raphael Y, Kohrman DC. Mutation of the novel gene Tmie results in sensory cell defects in the inner ear of spinner, a mouse model of human hearing loss DFNB6. Hum Mol Genet 2002; 11(16): 1887–1898.

    CAS  PubMed  Article  Google Scholar 

  21. Maeda R, Kindt KS, Mo W, Morgan CP, Erickson T, Zhao H, Clemens-Grisham R, Barr-Gillespie PG, Nicolson T. Tip-link protein protocadherin 15 interacts with transmembrane channellike proteins TMC1 and TMC2. Proc Natl Acad Sci USA 2014; 111(35): 12907–12912.

    CAS  PubMed  Article  Google Scholar 

  22. Xiong W, Grillet N, Elledge HM, Wagner TF, Zhao B, Johnson KR, Kazmierczak P, Müller U. TMHS is an integral component of the mechanotransduction machinery of cochlear hair cells. Cell 2012; 151(6): 1283–1295.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  23. Fettiplace R. Is TMC1 the Hair Cell Mechanotransducer Channel? Biophys J 2016; 111(1): 3–9.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  24. Lee Y, Chang SY, Jung JY, Ahn SC. Reinvestigation of cochlear pathology in circling mice. Neurosci Lett 2015; 594: 30–35.

    CAS  PubMed  Article  Google Scholar 

  25. Tang X, Zhu X, Ding B, Walton JP, Frisina RD, Su J. Age-related hearing loss: GABA, nicotinic acetylcholine and NMDA receptor expression changes in spiral ganglion neurons of the mouse. Neuroscience 2014; 259: 184–193.

    CAS  PubMed  Article  Google Scholar 

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Acknowledgments

This work was supported by the grants from Korea Ministry of Science, ICT and Future Planning to J. G. S. (KMPC:2014M3A9D5A01075129).

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Correspondence to Jun Gyo Suh.

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Kim, Y.Y., Nam, H., Jung, H. et al. Over-expression of myosin7A in cochlear hair cells of circling mice. Lab Anim Res 33, 1–7 (2017). https://doi.org/10.5625/lar.2017.33.1.1

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  • DOI: https://doi.org/10.5625/lar.2017.33.1.1

Keywords

  • Circling mice
  • cochlea
  • transmembrane inner ear (Tmie)
  • myosin7a