Elsevier

Brain Research

Volume 1091, Issue 1, 26 May 2006, Pages 16-26
Brain Research

Research Report
Auditory brainstem responses in 10 inbred strains of mice

https://doi.org/10.1016/j.brainres.2006.01.107Get rights and content

Abstract

The auditory brainstem response (ABR) is an evoked potential response of auditory activity in the auditory nerve and subsequent fiber tracts and nuclei within the auditory brainstem pathways. The threshold, amplitude, and latency analysis of the ABR provides information on the peripheral hearing status and the integrity of brainstem pathways. In this study, we compared the threshold, amplitude, and latency of ABRs recorded from 149 mice of 10 commonly used inbred strains (BALB/cJ, C3HeB/FeJ, C3H/HeJ, CAST/EiJ, CBA/CaJ, CBA/J, FVB/NJ, MRL/MpJ, NZB/BlNJ, and SJL/J) using clicks of different intensities. The ABR thresholds of these strains ranged from 32 to 43 dB SPL. The amplitude of both waves I and IV of ABRs, which increased monotonically with click intensity in most strains, differed significantly among different strains at each intensity tested. Moreover, the amplitude of both waves was inversely correlated with the body weight of each strain at most intensities tested. In general, the amplitude of wave IV was smaller than that of wave I resulting in the IV/I amplitude ratio of <1.0 in all strains. The peak latency of both waves I and IV decreased significantly with click intensity in each strain. However, this intensity-dependent decrease was greater for wave IV than for wave I such that the wave I–IV inter-peak latency also decreased significantly with increasing intensity. I–IV inter-peak latencies for MRL/MpJ, C3HeB/FeJ, NZB/BlNJ, and C3H/HeJ strains are longer than FVB/NJ, SJL/J, or CAST/EiJ. This work is the first step to study the genetic basis underlying strain-related differences in auditory pathway.

Introduction

The auditory brainstem response (ABR) is an evoked potential measurement of auditory activity in the auditory nerve and subsequent fiber tracts and nuclei within the auditory brainstem pathways. The threshold, amplitude, and latency analysis of the ABR provides information on the peripheral hearing status and the integrity of brainstem pathways. Therefore, the measurement of ABR has become a useful and practical procedure for the determination of hearing levels in animals and young children (Arnold, 2000, Musiek et al., 1994, Parham et al., 2001). In mice, the ABR threshold has been used successfully to estimate audiometric thresholds in hearing and genetic research (Davis et al., 2002, Duan and Canlon, 1996, Erway et al., 1996, Erway et al., 1993, Hirose and Liberman, 2003, Money et al., 1995, Munemoto et al., 1998, Rosowski et al., 2003, Szymko-Bennett et al., 2003). A PubMed search using key words of mouse, ABR, and threshold has revealed 80 of these studies since 1985.

The successful use of ABR threshold for assessment of the hearing sensitivity of mice has lead to strain characterization (Zheng et al., 1999), gene localization (Galambos and Hecox, 1978, Henry, 2004, Hirose and Liberman, 2003, Huang and Buchwald, 1978, Hunter and Willott, 1987, Ikeda et al., 2002, Ingham et al., 1998, Jimenez et al., 1999, Johnson et al., 2001), and gene identification (Ikeda et al., 2002, Johnson et al., 2000, Johnson et al., 2001, Johnson et al., 2003) since 1997. Moreover, the measurement of ABR threshold has proven essential in identifying modifier genes (Ikeda et al., 2002, Johnson and Zheng, 2002, Johnson et al., 2000, Johnson et al., 2001, Noben-Trauth et al., 1997, Noben-Trauth et al., 2003, Zheng and Johnson, 2001). However, previous studies have shown that, while some hearing impairments were characterized by significant changes in all ABR parameters such as the threshold, amplitude, and latency, others were associated with the abnormalities in the amplitude and latency but not the threshold (Evans et al., 1983, Fujiyoshi et al., 1994, Kanzaki et al., 1985). For example, Kanzaki et al. (1985) have shown that the peak latency of later ABR waves for the shiverer mice was prolonged with increased inter-peak latency although the threshold was normal. To further assess the hearing sensitivity with ABR, we have studied the ABR threshold as well as the variation in amplitude and latency of ABR components as a function of stimulus intensity in 10 different inbred strains of mice. These mouse strains include BALB/cJ, C3HeB/FeJ, C3H/HeJ, CAST/EiJ, CBA/CaJ, CBA/J, FVB/NJ, MRL/MpJ, NZB/BlNJ, and SJL/J. Because these strains are commonly used and readily available, they have become increasingly important for medical research since the gene mutations on these strain backgrounds provide models for a variety of human disorders. To our knowledge, the amplitude and latency of ABR components determined at different intensities have only been reported for CBA/CaJ and CBA/J mice among these strains (Burkard et al., 2001, Hunter and Willott, 1987).

Millions of mice are produced annually at the Jackson Laboratory. These mice belong to nearly 2800 strains of genetically defined and modified strains, including standard inbred strains, recombinant inbred strains, congenic inbred strains, and inbred strains carrying both spontaneous and induced mutations. The Neuroscience Mutagenesis Facility at the Jackson Laboratory has undertaken a large scale auditory screening project, which is specifically designed to provide novel murine genetic models for human deafness. The data reported in this study provide a reliable reference for evaluating mouse hearing in terms of amplitude and latency of ABR components. The strain differences in ABR parameters reported in this study suggest genetic determinants, which may lead to gene identification and novel mechanism discovery for the future studies.

Section snippets

Results

As described above, we used clicks and tone bursts to study the ABR threshold as well as the variation in amplitude and latency of ABR components as a function of stimulus intensity in 10 different inbred strains of mice. Because of the large amount of data, we mainly present ABR results obtained using click stimulation in this report. To address the issue of age-related hearing loss (AHL), which is characterized by a gradual decrease in sensitivity in the high to low frequency direction,

Discussion

As reported in previous studies (Chuu et al., 2001, Fujiyoshi et al., 1994, Hunter and Willott, 1987, Parham et al., 2001, Zheng et al., 1999), the ABR patterns of mice typically consisted of five vertical positive waves (Figs. 1A-1, B-1). Although the precise origins of ABR waves are not yet well defined, it is generally agreed that, in animal models such as cats, ferrets, non-human primates, and rodents, the first wave represents activities from the auditory nerve while the later waves

Animals

A total of 149 mice from 10 different inbred strains were used in this study. The strain names, age, and the number of mice tested in each strain are shown in Table 1. These mice were produced within the production facilities of the Jackson Laboratory. Prior to ABR recording, animals were anesthetized by intraperitoneal injection with Avertin (tribromoethanol stabilized in tertiary amyl hydrate) given at a dose of 5 mg tribromoethanol/10 g body weight. An otoscopic examination was then

Acknowledgments

The work was supported by grants MH067670, NSFC30440080, DC005846, and a grant from the Research Board of University of Missouri-Columbia (URB-03-057). We thank Melissa L Berry for critical review of the manuscript. We thank Dr. Weidong Zhang for statistical assistance.

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