Hearing Loss In Mice Research Articles

Progressive hearing loss in mouse models of presbycusis: Influence of an augmented acoustic environment and of gender

Progressive hearing loss associated with aging can be modulated by a number of genetic and environmental variables. Understanding how such variables work may suggest new approaches to ameliorate presbycusis. Two examples are long-term exposure to an augmented acoustic environment (AAE) and factors associated with gender (e.g., during the period of reproductive decline in females after 6 months of age). Research on inbred strains of mice that exhibit progressive hearing loss (C57BL/6J, BALB/cJ, DBA/2J) has demonstrated that daily exposure to a 70-dB SPL broadband noise AAE slows the progressive elevation of ABR thresholds, enhances behavioral responses to tones (startle response; prepulse inhibition), and affects histopathology of the cochlea and anteroventral cochlear nucleus (AVCN). However, gender plays a role in both the progression of hearing loss in nonexposed mice and the effects of the AAE. In the absence of AAE exposure, young C57BL/6J and BALB/cJ males and females have similar ABR thresholds, but hearing loss deteriorates more rapidly in females after around age 6 months. The auditory systems of males and females also respond differently to the AAE. Depending on gender, both positive and negative effects of AAE exposure are observed, although these effects are complicated.

Genetics of age-related hearing loss in mice. IV. Cochlear pathology and hearing loss in 25 BXD recombinant inbred mouse strains

The effects of three putative genes which contribute to age-related hearing loss (AHL genes) were evaluated using auditory brainstem response (ABR) thresholds and post-mortem cochlear histopathology in 25 recombinant BXD inbred mouse strains, originally derived from C57BL/6J (B6) and DBA/2J (D2) progenitor strains. All BXD strains showed substantial elevation of ABR thresholds and loss of spiral ganglion cells (SGCs) during the first year of life. The findings are consistent with our genetic model in which D2 and B6 inbred strains both possess the Ahl (age-related hearing loss) gene, whereas D2 possesses two additional chromosomal loci with AHL genes ( Ahl2 and Ahl3). The between-strain distribution in the severity of SGC loss and ABR threshold elevations suggests that the severity of hearing loss is determined in large part by the number of AHL genes an animal possesses and by additional genetic background effects. The present findings also demonstrate that, because BXD strains vary substantially in the rate and severity of progressive hearing loss (but are genetically closely related), they can provide powerful animal models for developmental studies of AHL.

Mdfw:A Deafness Susceptibility Locus That Interacts with Deaf Waddler (dfw)

The deaf waddler (dfw) mutation is a model system to study the biology of neuroepithelial hearing defects in mice. Here we describe the identification and characterization of a new allele of deaf waddler (dfw2J) and present evidence for a hearing susceptibility locus (mdfw) that interacts withdfw.We found that CBy-dfw2J/dfw2Jhomozygotes exhibit no discernible auditory brainstem responses (ABR) to sound pressure level stimuli up to 100 dB, indicating a profound deafness. Interestingly, the ABR in CBy-dfw2J/+ heterozygotes is also abnormal, showing age-dependent elevated thresholds characteristic of a progressive hearing loss. When outcrossed onto the CAST/Ei strain, only 24% of the F2 CBy/CAST-dfw2J/+ heterozygotes displayed increased ABR thresholds, suggesting that a second locus, controlling hearing function indfw2J/+ heterozygotes, was segregating in the CBy/CAST-dfw2Jintercross. By linkage analysis, we localized this locus (mdfw) to Chromosome 10, between markersD10Mit127andD10Mit185,within a 4.0 ± 1.1 cM genetic interval. All CBy/CAST-dfw2J/+ heterozygotes that develop hearing loss are homozygous for the CBy-derived recessive allele (mdfwC). In contrast, CBy/CAST-dfw2J/+ heterozygotes expressing even a single copy of the CAST/Ei-derivedmdfwallele (Mdfw) retain their normal hearing function. Our results reveal an epistatic relationship between themdfwand thedfwgenes and provide a model system to study nonsyndromic hearing loss in mice.

Genetics of age-related hearing loss in mice. III. Susceptibility of inbred and F1 hybrid strains to noise-induced hearing loss

Some humans and mice are genetically predisposed to age-related hearing loss (AHL), and others are variously susceptible to noise-induced hearing loss (NIHL). The inbred C57BL/6J (B6) mice exhibit AHL at an early age, whereas the inbred CBA/CaJ (CB) mice do not. The B6 mice are much more susceptible to NIHL than are the CB mice (Shone et al., 1991; Li, 1992a). The B6 mice possess an Ahl gene which maps to chromosome 10 (Erway et al., 1995). This study was designed, using these two inbred strains plus two F1 hybrid strains of mice, to begin to test the hypothesis that the Ahl genotypes may influence the susceptibility to NIHL. These strains of mice (with putative genotypes) are: inbred CB (+/+) and B6 ( Ahl/Ahl); hybrid CBB6F1 (+/ Ahl) and B6D2F1 ( Ahl/Ahl; D2 represents inbred DBA/2J). Twenty-four mice of each of these four strains were exposed to noise (110 dB for 0, 1 or 2 h) and tested for auditory-evoked brainstem response (ABR) thresholds. The CB and CBB6F1 strains of mice did not differ significantly from each other, exhibiting mostly temporary threshold shifts. The B6 and B6D2F1 strains of mice did not differ significantly from each other, but did exhibit permanent threshold shifts. These results support the hypothesis that genetic predisposition to AHL may be revealed at a younger age by NIHL. This suggests that it may be possible to use the NIHL to distinguish segregating genotypes (+/ Ahl vs. Ahl/Ahl) backcross progeny and thereby to identify and map single genes for AHL.

Genetics of age-related hearing loss in mice. II. Strain differences and effects of caloric restriction on cochlear pathology and evoked response thresholds

The effects of genotype and diet on age-related hearing loss were evaluated using auditory brainstem response (ABR) thresholds and post-mortem cochlear histopathology in 5 inbred mouse strains, CBA/H-T6J (CH), DBA/2J (D2), C57BL/6J (B6), BALB/cByJ (BY) and WB/ReJ (WB), and their 10 F1 hybrid strains. The mice had been maintained since weaning on either a high-energy (HE) control diet or low-energy (LE) calorically restricted diet. ABR thresholds were obtained when the mice were 23 months old; the mice were allowed to age until they died from natural causes prior to obtaining the histological material. The severity of post-mortem cochlear pathology in mice maintained with the HE diet supports our earlier genetic model which postulated that B6, BY, and WB strains each possessed a different recessive allele causing age-related hearing loss, D2 mice possessed all 3 genes, and CH mice possessed none. The histopathology indicates that the genes act at the cochlear level. Dietary restriction resulted in increased longevity in a number of strains, but age-related changes in cochlear pathology were not ameliorated in any of these; indeed, in some strains long-lived LE mice exhibited severe cochlear degeneration. In strains for which longevity was not extended by caloric restriction, only B6 mice exhibited an ameliorative effect of the LE diet on cochlear pathology. ABRs in 23-month-olds indicated a slowing of age-related hearing loss in LE mice of 3 F1 hybrid strains.

Genetics of age-related hearing loss in mice: I. Inbred and F1 hybrid strains

The auditory-evoked brainstem response (ABR) was used to assess hearing loss in five inbred strains of mice and all ten combinations of F1 hybrids. The inbred strains are CBA/H-T6J (CH), DBA/2J (D2), C57BL/6J (B6), BALB/cByJ (BY) and WB/ReJ (WB). The F1 hybrids are CHD2, CHB6, CHBY, CHWB, D2B6, D2BY, D2WB, B6BY, B6WB, and BYWB. At middle age (12, 16 months), mice were tested with click stimuli. At a relatively old age (23 months, near inbreds' median life span), they were tested with both click and tone-pip stimuli. The CH mice and their four F1 hybrid strains exhibit lower thresholds than the other strains, with the F1 strains being most sensitive (i.e., hybrid vigor). The D2 inbred and the three D2 F1 hybrids (excluding CHD2) exhibit the earliest and most severe hearing losses. The B6, BY and WB inbred strains exhibit severe hearing losses between 16 and 23 months of age; however, the B6BY, B6WB and BYWB F1 hybrids have significantly lower thresholds than their parental strains (genetic complementation). These data support a genetic model for recessive alleles at three different loci which contribute to age-related hearing loss. The CH mice have none of the recessive alleles, and the D2 mice are homozygous recessive for all three; the B6, BY and WB inbred strains are homozygous recessive respectively for one of the three loci.

Reversible Conductive Hearing Loss in Mice

Fibrin tissue adhesive was injected into the right ears of four 7-week-old CBA/J mice. Auditory brain stem responses (ABRs) were used to monitor changes in auditory sensitivity over the next 26 days, after which the middle ears and cochleas were examined histologically. Mean maximum ABR threshold shifts were as great as 36 dB, and were larger for higher frequencies than for lower. Maximum shifts occurred between 1 and 8 days; by 26 days, thresholds had returned to intensity levels observed before injection.

Age-dependent changes in susceptibility to ototoxic hearing loss.

Several species undergo age-dependent changes in susceptibility to noise-induced and drug-induced hearing loss. In this experiment 18-day-old mice were given 200 mg/kg kanamycin plus varying doses of bumetanide (20, 30 or 40 mg/kg). Thresholds of the scalp-recorded compound action potential of the auditory nerve indicated that diuretic doses of 30 and 40 mg/kg produced significant loss of hearing sensitivity. Thirty-eight-day-old mice were then treated with 200 mg/kg kanamycin plus 40 mg/kg bumetanide and demonstrated no loss of hearing sensitivity. These results confirm the existence of age-dependent changes in susceptibility to ototoxic hearing loss in mice. Furthermore, the treatment, consisting of two injections on the same day, offers promise as a means of defining the critical period of susceptibility in greater detail than has been possible with aminoglycosides alone.

Comparison of response properties of inferior colliculus neurons of two inbred mouse strains differing in susceptibility to audiogenic seizures.

Comparison of response properties of inferior colliculus neurons of two inbred mouse strains differing in susceptibility to audiogenic seizures.J F WillottJ F WillottPublished Online:01 Jan 1981https://doi.org/10.1152/jn.1981.45.1.35MoreSectionsPDF (2 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByBreed differences in cochlear integrity in adult, commercially raised chickensHearing Research, Vol. 166, No. 1-2Fear conditioning in C57/BL/6 and DBA/2 mice: variability in nucleus accumbens function according to the strain predisposition to show contextual- or cue-based respondingEuropean Journal of Neuroscience, Vol. 12, No. 12Sound-induced seizures in serotonin 5-HT2c receptor mutant mice1 August 1997 | Nature Genetics, Vol. 16, No. 4Responses of inferior colliculus neurons in C57BL/6J mice with and without sensorineural hearing loss: Effects of changing the azimuthal location of an unmasked pure-tone stimulusHearing Research, Vol. 78, No. 2Responses of inferior colliculus neurons in C57BL/6J mice with and without sensorineural hearing loss: Effects of changing the azimuthal location of a continuous noise masker on responses to contralateral tonesHearing Research, Vol. 78, No. 2Morphology of the cochlear nucleus in CBA/J mice with chronic, severe sensorineural cochlear pathology induced during adulthoodHearing Research, Vol. 74, No. 1-2GABA in the inferior colliculus plays a critical role in control of audiogenic seizuresBrain Research, Vol. 640, No. 1-2Stimulation or blockade of the dorsal nucleus of the lateral lemniscus alters binaural and tonic inhibition in contralateral inferior colliculus neuronsHearing Research, Vol. 69, No. 1-2Genetics of age-related hearing loss in mice: I. Inbred and F1 hybrid strainsHearing Research, Vol. 65, No. 1-2Involvement of GABA in acoustically-evoked inhibition in inferior colliculus neuronsHearing Research, Vol. 52, No. 1Effect of GABA (γ-aminobutyric acid) on neurotransmission in inferior colliculus slices from the guinea pigNeuroscience Research, Vol. 6, No. 5Aging and the auditory brainstem response in mice with severe or minimal presbycusisHearing Research, Vol. 30, No. 2-3Decreased effectiveness of GABA-mediated inhibition in the inferior colliculus of the genetically epilepsy-prone ratExperimental Neurology, Vol. 93, No. 1Neuronal response abnormalities in the inferior colliculus of the genetically epilepsy-prone ratElectroencephalography and Clinical Neurophysiology, Vol. 63, No. 3The acoustic startle response in DBA/2 and C57BL/6 mice: relationship to auditory neuronal response properties and hearing impairmentHearing Research, Vol. 16, No. 2Frequency difference limens of C57BL/6 and DBA/2 mice: relationship to auditory neuronal response properties and hearing impairmentHearing Research, Vol. 16, No. 2Changes in frequency representation in the auditory system of mice with age-related hearing impairmentBrain Research, Vol. 309, No. 1Inferior colliculus single unit responses to peripheral electrical stimulation in normal and congenitally deaf miceDevelopmental Brain Research, Vol. 15, No. 1Abnormal tonotopic organization in the ventral cochlear nucleus of the hearing-impaired DBA/2 mouseNeuroscience Letters, Vol. 34, No. 1 More from this issue > Volume 45Issue 1January 1981Pages 35-47 https://doi.org/10.1152/jn.1981.45.1.35PubMed7205343History Published online 1 January 1981 Published in print 1 January 1981 Metrics