Acoustic injury in mice: 129/SvEv is exceptionally resistant to noise-induced hearing loss
Introduction
The large inter-subject variability in acoustic injury in a variety of species, including humans, has suggested that, within a given population, some have ‘tough’ while others have ‘tender’ ears, although the mechanisms underlying such differences are poorly understood (Cody and Robertson, 1983). In mouse models of acoustic injury, there appears to be more homogeneity in vulnerability across animals within a given strain; presumably because of the greater degree of genetic homogeneity in inbred mouse strains than in other commonly used experimental animals (Liberman, unpublished). On the other hand, significant inter-strain differences in susceptibility to noise-induced hearing loss (NIHL) have been reported (Li et al., 1993, Erway et al., 1996). Given the expanding knowledge of the mouse genome, such inter-strain phenotypic differences can be exploited to isolate the genes responsible. For example, the C57Bl/6 strain of mice is significantly more vulnerable to acoustic injury than the CBA/Ca strain. The fact that C57Bl/6 mice also show dramatic age-related hearing loss (AHL) compared to the CBA/Ca strain has suggested that the same inter-strain genetic difference is responsible for both AHL and NIHL enhancements in the C57Bl/6 phenotype (Erway et al., 1996). If such inter-strain differences are caused by differences in a single gene locus, as appears to the case for the AHL phenotype in C57BL/6, genetic back-crossing experiments can be performed to map the chromosomal locus, and ultimately to identify the gene product involved (Johnson et al., 1997).
We recently began a study of acoustic injury in another strain of mice, 129/SvEv. This strain is popular for creation of targeted gene deletions, or ‘knockouts’. Indeed, it was the availability of a particularly interesting knockout mouse, lacking the α9 cholinergic receptor on outer hair cells, which instigated our investigation of NIHL in 129/SvEv (Vetter et al., 1999). In the course of establishing the vulnerability of wild-type 129 mice, we noted that this strain was exceptionally resistant to acoustic injury, even though it may also suffer from AHL (Zheng et al., 1999). The present report documents baseline auditory function, both with respect to middle-ear transmission and cochlear thresholds, in untreated 129/SvEv mice as compared with CBA/Ca mice, the ‘gold standard’ normal-hearing strain of mouse. We then demonstrate the exceptional resistance of the 129/SvEv mice to acoustic overexposure, as assessed by either physiological or histopathological measures, and suggest that the relevant differences lie in the cochlea rather than in middle-ear transmission.
Section snippets
Experimental groups and experimental design
Experimental animals were male mice of CBA/CaJ (Jackson Laboratory, ME, USA) or 129/SvEv (Taconic, NY, USA; Nomenclature changed in 1998 to 129S6/SvEvTac). All animals were tested physiologically at 10–11 weeks of age (23–29 g) in a terminal procedure to evaluate either middle-ear transmission or cochlear function. In selected animals, cochleas were fixed and harvested for histological analysis. All procedures were approved by the IACUC of the Massachusetts Eye and Ear Infirmary.
From each
Cochlear function
In unexposed mice, CAP thresholds in the two strains were within 10 dB at test frequencies <30 kHz, although 129/SvEv was systematically less sensitive (Fig. 1A). At high frequencies (>30kHz), CAP thresholds in 129/SvEv begin to deviate more significantly from that of CBA/CaJ. Note that the interanimal variability is quite low: each point in Fig. 1A has standard error bars, many of which are hidden by the symbol thickness. Thus, although the interstrain differences were small, they were highly
Differences in vulnerability to acoustic injury
The literature on acoustic injury is in substantial agreement on the general observation that, above a critical sound pressure, NIHL usually grows very rapidly. The present data for the CBA/CaJ mouse was consistent with this trend: a 2 h exposure at 97 dB SPL caused only a 5 dB PTS, whereas only a 3 dB increase in the exposure level (to 100 dB SPL) resulted in a 35 dB increase in the maximum PTS (Fig. 3, Fig. 5). A further 3 dB increase in exposure level (to 103 dB) caused an additional 15 dB
Acknowledgements
This work was supported by Grants from the NIDCD: RO1 DC-0188 (M.C.L.) and R01 DC 00194 (J.J.R.).
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