Reproductive and Developmental Biology

The Korean Society of Animal Reproduction (한국동물번식학회)
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Introduction of tmie Gene Can Recover the Hearing Impairment and Abnormal Behavior in the Circling Mouse

  • Shin, Mi-Jung (School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University) ;
  • Park, Seo-Jin (School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University) ;
  • Pare, Hum Dai (Department of Biotechnology, School of Engineering, Daegu University) ;
  • Ryoo, Zae-Young (School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University)
  • Received : 2010.05.10
  • Accepted : 2010.06.05
  • Published : 2010.06.30
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Abstract

The spontaneous mutant circling mouse (cir/cir) shows a circling behavior and hearing loss. We produced transgenic mice overexpressing transmembrane inner ear (tmie) gene, the causative gene, for the phenotypic rescue of the circling mouse. Through the continuous breeding with circling mice, the cir/cir homozygous mice carrying the transgene (cir/cir-tg) were produced. The rescued cir/cir-tg mice were able to swim in the water with proper orientation and did not show any circling behavior like wild type mice. Western blot and immunohistochemical analysis exhibited that the transgenic tmie was expressed in the inner ear. Inner and outer hair cells were recovered in the cochlea and spiral ganglion neurons were also recovered in the rescued mice. Auditory brainstem response (ABR) test demonstrated that the cir/cir-tg mice are able to respond to sound. This study demonstrates that tmie transgene can recover the hearing impairment and abnormal behavior in the circling mouse.

Keywords

Acknowledgement

Supported by : Korea Science and Engineering Foundation (KOSEF)

References

  1. Snell GD, Law LW (1939): A linkage between shaker-2 and wavy-2 in the house mouse. J Hered 30:447. https://doi.org/10.1093/jhered/30.10.447
  2. Kaiser A, Fedrowitz M, Ebert U, Zimmnermann E, Hedrich HJ, Wedekind D, Loscher W (2001): Auditory and vestibular defects in the circling (ci2) rat mutant. Eur J Neurosci 14:1129-1142. https://doi.org/10.1046/j.0953-816x.2001.01726.x
  3. Lee JW, Ryoo ZY, Lee EJ, Hong SH, Chung WH, Lee HT, Chung KS, Kim TY, Oh YS, Suh JG (2002): Circling mouse, a spontaneous mutant in the innerear. Exp Anim 51:167-171. https://doi.org/10.1538/expanim.51.167
  4. Lee JW, Lee EJ, Hong SH, Chung WH, Lee HT, Lee TW, Lee JR, Kim HT, Suh JG, Kim TY, Ryoo ZY (2001): Circling mouse: possible animal model for deafness. Comp Med 51:550-554.
  5. Chung WH, Kim KR, Cho YS, Cho DY, Woo JH, Ryoo ZY, Cho Kl, Hong SH (2007): Cochlear pathology of the circling mouse: a new mouse model of DFNB6. Acta Otolaryngol 127:244-251. https://doi.org/10.1080/00016480600827071
  6. Probst FJ, Fridell RA, Raphael Y, Saunders TL, Wang A, Liang Y, Morell RJ, Touchman JW, Lyons RH, Noben-Trauth K, Friedman TB, Camper SA (1998): Correction of deafness in shaker-2 mice by an unconventional myosin in a BAC transgene. Science 280:1444-1447. https://doi.org/10.1126/science.280.5368.1444
  7. Lalwani AK, Castelein CM (1999): Cracking the auditory genetic code: Nonsyndromic hereditary hearing impairments. Am J Otol 20:115-132.
  8. Spoendlin H (1971): Degeneration behavior of the cellular nerve. Arch Klin Exp Ohren Nasen Kehlkopfheilkd. 200:275-291. https://doi.org/10.1007/BF00373310
  9. Su MC, Yang JJ, Chou MY, Hsin CH, Su CC, Li SY (2008): Expression and localization of tmie in adult rat cochlea. Histochem Cell Biol 130:119-126. https://doi.org/10.1007/s00418-008-0385-z
  10. Ishimoto S, Kawamoto K, Kanzaki S, Raphael Y (2002): Gene transfer into supporting cells of the organ of Corti. Hear Res 173:187-197. https://doi.org/10.1016/S0378-5955(02)00579-8
  11. Ryals BM, Rubel EW (1988): Hair cell regeneration after acoustic trauma in adult Cotrunix quail. Science 240:1774-1776. https://doi.org/10.1126/science.3381101
  12. Woolley SM, Wissman AM, Rubel EW (2001): Hair cell regeneration and recovery of auditory thresholds following aminoglycoside ototoxicity in Bengales finches. Hear Res 153:181-195. https://doi.org/10.1016/S0378-5955(00)00217-3
  13. Kawmnoto K, Ishimoto S, Minoda R, Brough DE, Raphael Y (2003): Math1 gene transfer generates new cochlear hair cells in mature guinea pigs in vivo. J Neurosci 23:4395-4400.
  14. Mitchem KL, Hibbard E, Beyer LA, Bosom K Dootz GA, Dolan DF, Johnson KR, Raphael Y, Kohrman DC (2002): 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 11:1887-1898. https://doi.org/10.1093/hmg/11.16.1887
  15. Krogh A, Larsson B, von Heijne G, Sonnhammer EL (2001): Predicting transmembrane protein topology with a hidden Markov model: application to complete genomes. J Mol Biol 305:567-580. https://doi.org/10.1006/jmbi.2000.4315
  16. Corwin JT, Cotanche DA (1988): Regeneration of sensory hair cells after acoustic trauma. Science 240:1772-1774. https://doi.org/10.1126/science.3381100
  17. Spoendlin H (1975): Retrograde degeneration of the cochlear nerve. Acta Otolaryngol 79:266-275. https://doi.org/10.3109/00016487509124683
  18. Webster M, Webster DB (1981): Spiral ganglion neuron loss following organ of Corti loss: a quantitative study. Brain Res 212:17-30. https://doi.org/10.1016/0006-8993(81)90028-7
  19. Liu JJ, Shin JH, Hyrc KL, Liu S, Lei D, Holley MC, Bao J (2006): Stem cell therapy for hearing loss: Math1 overexpression in VOT-E36 cells. Otol Neurotol 27:414-421. https://doi.org/10.1097/00129492-200604000-00020
  20. Minoda R, Izurnikawa M, Kawmnoto K, Raphael Y (2004): Strategies for replacing lost cochlear hair cells. Neuroreport 15:1089-1092. https://doi.org/10.1097/00001756-200405190-00001
  21. Deol MS (1952): The anomalies of the labyrinth of the mutants varitintwaddler, shaker-2 and jerker in the mouse. J Genet 52:562-588.
  22. Cho Kl, Suh JG, Lee JW, Hong SH, Kang TC, Oh YS, Ryoo ZY (2006): the circling mouse (cir/cir-C-57BL6) has a 40-kilobase genomic deletion that includes the transmembrane inner ear (tmie) gene. Comp Med 56:476-481.
  23. Kanzaki S, Beyer L, Karolyi IJ, Dolan DF, Fang Q, Probst FJ, Camper SA, Raphael Y (2006): Transgene correction maintains normal cochlear structure and function in 6-month-old Myo15a mutant mice. Hear Res 214:37-44. https://doi.org/10.1016/j.heares.2006.01.017