Males lose hearing earlier in mouse models of late-onset age-related hearing loss; females lose hearing earlier in mouse models of early-onset hearing loss
Introduction
Men are often described as having auditory functions that are less sensitive than those of women (Rosen et al., 1964, Northern et al., 1972). These differences are most evident in detection thresholds of high frequency stimuli, with males becoming progressively less sensitive as they age (Corso, 1963, Gates et al., 1990). These changes of the male’s hearing have been attributed to genetics, environmental factors, and/or the interaction of these variables (Pederson et al., 1989, Reardon, 1990, Pearson et al., 1995, Gates et al., 1999, Tambs et al., 2003). Even though both ethical and practical considerations restrict our ability to experimentally evaluate the relative contributions of these variables on gender differences of human hearing, an appropriate animal model might allow us to circumvent these restrictions.
Inbred mice have been widely used as models of age-related hearing loss. The C57BL/6 strain has been most extensively studied as a model of early-onset hearing loss (Mikaelian et al., 1974, Henry and Lepkowski, 1978, Mikaelian, 1979, Henry and Chole, 1980). Anatomically, physiologically and behaviorally, these mice display cochlear dysfunctions, progressing from high to lower frequencies. Pathological changes are evident by puberty and progressively increase with age (Henry, 1979, Henry and Chole, 1980, Shnerson and Pujol, 1983).
By contrast, the CBA inbred strain has long been considered a normal hearing mouse (Berlin, 1963, Alford and Ruben, 1964, Mikaelian et al., 1965, Birch et al., 1968). This genotype only shows significant cochlear losses at extreme old age, well past its actuarial lifespan (Henry and Chole, 1980). Not surprisingly, the CBA genotype has been considered a model of late-onset hearing loss, and its auditory functions have often been compared with those of the C57BL/6. A Medline search revealed 30 of these comparison studies since 1978 (e.g., Henry, 1984, Willott, 1986, Willott et al., 1987, Brown et al., 1995, Spongr et al., 1997, Sun and Kim, 1999, Ding et al., 1999).
A report by McGinn et al. (1992) described the closely related CBA/Ca mouse as being less susceptible than the CBA to otitis media. Li and Borg (1991) had earlier shown the CBA/CaJ to express hearing loss late in life, and subsequently this genotype was more often compared with the C57BL/6. A Medline search found 20 of these comparison studies since 1992 (e.g., Li and Hultcrantz, 1994, Erway et al., 1996, O’Neill et al., 1997, Miller et al., 1998, Jimenez et al., 1999, Ohlemiller et al., 2000).
Recently, gender has been reported to influence the early-onset presbycusis of the C57BL/6 mouse (Henry, 2002), with females showing earlier and more extensive losses than males. Because this effect is contrary to the pattern seen in humans, this finding could be interpreted as evidence that this mouse model is less suitable than had been previously thought. The present study was conducted to look for gender effects in the CBA and CBA/Ca models of late-onset hearing loss, and to compare these results with those from the C57BL/6. The results consistently show that male CBA and CBA/Ca mice have poorer high frequency cochlear function than females of these lines, and replicate the earlier findings that male C57BL/6 mice have better hearing than females of this genotype.
Section snippets
Methods
Thirty CBA/J, 33 C57BL/6J, and 59 CBA/CaJ inbred mice were used for these experiments. They ranged in age from 50 to 350 days, although within a single comparison the ages of the animals varied by no more than ±4 days. They were bred and maintained in a noise-controlled breeding colony under standard conditions. These mice were the first or second generation derived from stock that originated at the Jackson Laboratory (the J at the end of their strain name indicates their origin from that
Results
Fig. 1 shows the mean audiograms of postpubertal (50 day old) CBA/J mice, as determined by the minimal detection thresholds of the ABR generated by rapid rise time tone pips. As determined with this quasi-free-field stimulus presentation, the females have significantly more sensitive high frequency (24 kHz to 64 kHz) thresholds than the males. Because this genotype maintains its hearing until very near the end of its actuarial lifespan (Henry and Chole, 1980), this gender-specific pattern would
Discussion
This paper is the first to report that, in both the CBA/J and CBA/CaJ inbred strains of mice, males have poorer high frequency thresholds than females. This appears to mimic the pattern of hearing observed in humans. In the CBA/J mouse, this can be observed shortly after puberty (Fig. 1). This is not a developmental difference, because cochlear function is mature before 45 days of age in this strain (Henry and Chole, 1980, Henry, 1984). Nor is it an artifact of the extremely fast rise and fall
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2022, Hearing ResearchCitation Excerpt :This difference in cochlear nerve envelope response thresholds in aging C57BL/6J mice has been linked to greater outer hair cell loss and spiral ganglion cell loss in female cochleae (Willott and Bross, 2004). In contrast, CBA/J and CBA/CaJ mice, which do not carry the Ahl allele, show better hearing sensitivity in females at a young age (Henry, 2004). However, at around 18 to 24 months, female mice overtake males in the auditory decline (Ohlemiller et al., 2010).