Article thumbnail

Gipc3 mutations associated with audiogenic seizures and sensorineural hearing loss in mouse and human

By Nikoletta Charizopoulou, Andrea Lelli, Margit Schraders, Kausik Ray, Michael S. Hildebrand, Arabandi Ramesh, C. R. Srikumari Srisailapathy, Jaap Oostrik, Ronald J. C. Admiraal, Harold R. Neely, Joseph R. Latoche, Richard J. H. Smith, John K. Northup, Hannie Kremer, Jeffrey R. Holt and Konrad Noben-Trauth

Abstract

Sensorineural hearing loss affects the quality of life and communication of millions of people, but the underlying molecular mechanisms remain elusive. Here, we identify mutations in Gipc3 underlying progressive sensorineural hearing loss (age-related hearing loss 5, ahl5) and audiogenic seizures (juvenile audiogenic monogenic seizure 1, jams1) in mice and autosomal recessive deafness DFNB15 and DFNB95 in humans. Gipc3 localizes to inner ear sensory hair cells and spiral ganglion. A missense mutation in the PDZ domain has an attenuating effect on mechanotransduction and the acquisition of mature inner hair cell potassium currents. Magnitude and temporal progression of wave I amplitude of afferent neurons correlate with susceptibility and resistance to audiogenic seizures. The Gipc3343A allele disrupts the structure of the stereocilia bundle and affects long-term function of auditory hair cells and spiral ganglion neurons. Our study suggests a pivotal role of Gipc3 in acoustic signal acquisition and propagation in cochlear hair cells

Topics: Article
Publisher: Nature Publishing Group
OAI identifier: oai:pubmedcentral.nih.gov:3105340
Provided by: PubMed Central

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.

Suggested articles

Citations

  1. (2006). A . Binding of internalized receptors to the PDZ domain of GIPC/synectin recruits myosin VI to endocytic vesicles .
  2. (1986). A . Evidence for hair cell degeneration as the primary lesion in hearing loss of the elderly .
  3. (2008). a e r
  4. a GTPase-activating protein for Galphai heterotrimeric G proteins, is located on clathrin-coated vesicles .
  5. (2003). A h m e d
  6. (2001). A novel gene causing a mendelian audiogenic mouse epilepsy .
  7. (1998). a PDZ domain containing protein, interacts specifi cally with the C terminus of RGSGAIP .
  8. (2006). Acceleration of age-related hearing loss by early noise exposure: evidence of a misspent youth .
  9. (2003). Association of cadherin 23 with polygenic inheritance and genetic modifi cation of sensorineural hearing loss .
  10. (1999). Au t i s m a n d hearing loss .
  11. (1995). Av r a h a m
  12. (2006). BDNF-mediated neurotransmission relies upon a myosin VI motor complex .
  13. (2001). C h a o , M . V . & F a r q u h a r ,
  14. (1997). C h e n , A . et al. New gene for autosomal recessive non-syndromic hearing loss maps to either chromosome 3q or 19p .
  15. Chemical synaptic transmission in the cochlea .
  16. (1996). D o y l e , D . A . et al. Crystal structures of a complexed and peptide-free membrane protein-binding domain: molecular basis of peptide recognition by PDZ .
  17. (1997). Description and primary results from an audiometric study of male twins .
  18. Developmental and genetic audiogenic seizure models: behavior and biological substrates .
  19. (2003). Developmental changes in the expression of potassium currents of embryonic, neonatal and mature mouse inner hair cells .
  20. (1980). e n r y , K . R . & C h o l e , R . A . G e n o t y p i c d i ff erences in behavioral, physiological and anatomical expressions of age-related hearing loss in the laboratory mouse .
  21. (2002). GIPC gene family .
  22. (2002). GIPC participates in G protein signaling downstream of insulin-like growth factor 1 receptor .
  23. (2009). H e i d r y c h
  24. (2001). h r i s t e n s e n , K . , F r e d e r i k s e n , H . & H o ff
  25. (2008). Hair cell aff erent synapses .
  26. (2010). Homozygosity mapping reveals mutations of GRXCR1 as a cause of autosomal-recessive nonsyndromic hearing impairment .
  27. Increased perception of loudness in autism .
  28. (2009). Inheritance patterns of progressive hearing loss in laboratory strains of mice .
  29. (1998). l l o t t
  30. (1996). M e l c h e r
  31. (2002). M i s a w a , H . et al. I d e n t i fi cation of a monogenic locus (jams1) causing juvenile audiogenic seizures in mice .
  32. (2006). Mapping quantitative trait loci for hearing loss
  33. mutation underlies early onset hearing impairment in BUB/BnJ mice, a model for the auditory pathology of Usher Syndrome IIC .
  34. (2005). NIH Swiss and Black Swiss mice have retinal degeneration and performance defi cits in cognitive tests .
  35. Pe t e r s
  36. (2005). R e e d
  37. (2009). r i e d m a n , R . A . et al. GRM7 variants confer susceptibility to age-related hearing impairment .
  38. (2009). R o u x , I . et al. Myosin VI is required for the proper maturation and function of inner hair cell ribbon synapses .
  39. (2008). S e a l
  40. (2010). S h i n
  41. (2010). Statistics and epidemiology , www.nidcd.nih.gov (
  42. (2007). Th e role of the PDZ protein GIPC in regulating NMDA receptor traffi cking .
  43. (1998). Z i fk in ,