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Status |
Public on Sep 01, 2008 |
Title |
Noise-Induced Changes in Gene Expression in the Cochleae of Mice Differing in Their Susceptibility to Noise Damage |
Organism |
Mus musculus |
Experiment type |
Expression profiling by array
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Summary |
The molecular mechanisms underlying the great differences in susceptibility to noise-induced hearing loss (NIHL) exhibited by both humans and laboratory animals are unknown. Using microarray technology, the present study demonstrates that the effects of noise overexposure on the expression of molecules likely to be important to the development of NIHL differ among inbred mice that have distinctive susceptibilities to NIHL including B6.CAST, 129X1/SvJ, and 129S1/SvImJ. The noise-exposure protocol produced, on average, a permanent loss of about 40 dB in sensitivity for auditory brainstem responses in susceptible B6.CAST mice, but no threshold elevations for the two resistant 129S1/SvImJ and 129X1/SvJ substrains. Measurements of noise-induced gene expression changes 6 h after the noise exposure revealed significant alterations in the expression levels of 48 genes in the resistant mice, while by these same criteria, there were seven differentially expressed genes in the susceptible B6.CAST mice. Differentially expressed genes in both groups of mice included subsets of transcription factors. However, only in the resistant mice was there a significant induction of proteins involved in cell-survival pathways such as HSP70, HSP40, p21, GADD45beta, Ier3, and Nf-kappaB. Moreover, increased expression of three of these factors after noise was confirmed at the protein level. Drastically enhanced HSP70, GADD45beta, and p21 immunostaining were detected 6 h after the noise exposure in subsets of cells of the lateral wall, spiral limbus, and organ of Corti as well as in cochlear nerve fibers. Upregulation of these proteins after noise exposure likely contributes to the prevalence of survival cellular pathways and thus to the resistance to NIHL that is characteristic of the 129X1/SvJ mice. Keywords: effects of noise exposure in distinct inbred mice
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Overall design |
Female 10-wk-old mice of the B6.CAST and 129X1/SvJ strains were divided randomly into non-noise control and noise-exposure groups. The non-noise mice served as controls in the gene-profiling experiments to control for the stress induced by experimenter handling and/or confinement of the mice in the noise-exposure chamber that was not directly related to the noise. This mice were in the noise chamber for a sham exposure. In contrast, the ‘noise’ groups were exposed to a 105-dB SPL, 10-kHz octave band of noise for 1 h and sacrificed 6 h after the exposure. Of each of these major groups, eight mice were used for each of three 129X1/SvJ control and three noise-exposed 129X1/SvJ arrays and two B6.CAST control and two noise-exposed B6.CAST arrays. Consequently within each subgroup the arrays are biological replicates.
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Contributor(s) |
Gratton MA, Garcia J, Verduzco E, Martin GK, Lonsbury–Martin BL, Eleftheriadou A, Vázquez AE |
Citation(s) |
21187137 |
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Submission date |
Jun 30, 2007 |
Last update date |
Feb 18, 2018 |
Contact name |
Ana Elena Vazquez |
E-mail(s) |
avazquez@ucdavis.edu
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Phone |
530 752 2890
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Fax |
530 754 5046
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Organization name |
University of California, Davis
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Department |
Otolaryngology-Head and Neck Surgery
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Street address |
1515 Newton Court
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City |
Davis |
State/province |
CA |
ZIP/Postal code |
95618 |
Country |
USA |
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Platforms (1) |
GPL81 |
[MG_U74Av2] Affymetrix Murine Genome U74A Version 2 Array |
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Samples (10)
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Relations |
BioProject |
PRJNA101347 |
Supplementary file |
Size |
Download |
File type/resource |
GSE8342_RAW.tar |
40.7 Mb |
(http)(custom) |
TAR (of CEL, CHP) |
Processed data included within Sample table |
Processed data provided as supplementary file |
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