Age-related auditory pathology in the CBA/J mouse.

Commercially obtained aged male CBA/J mice presented a complex pattern of hearing loss and morphological changes. A significant threshold shift in auditory brainstem responses (ABR) occurred at 3 months of age at 4 kHz without apparent loss of hair cells, rising slowly at later ages accompanied by loss of apical hair cells. A delayed high-frequency deficit started at 24 kHz around the age of 12 months.

Dietary thyroid hormone replacement ameliorates hearing deficits in hypothyroid mice.

Thyroid hormone (TH) insufficiency causes variable hearing impairment and mental deficiency in humans. Rodents lacking TH have congenital hearing deficiency that has been attributed to physiologic, morphologic, and developmental abnormalities of the auditory system. We examined four genetically defined strains of hypothyroid mice for development of hearing and response to TH replacement initiated during late gestation and continued through six weeks of age.

Heat shock factor 1-deficient mice exhibit decreased recovery of hearing following noise overstimulation.

Heat shock proteins (Hsps) can enhance cell survival in response to stress. Heat shock factor 1 (Hsf1) is the major transcription factor that regulates stress-inducible Hsp expression. We previously demonstrated the presence of Hsf1 in the rodent cochlea and also demonstrated that a heat shock known to precondition the cochlea against noise trauma results in Hsf1 activation in the rodent cochlea.

Myo15 function is distinct from Myo6, Myo7a and pirouette genes in development of cochlear stereocilia.

The unconventional myosin genes Myo15, Myo6 and Myo7a are essential for hearing in both humans and mice. Despite the expression of each gene in multiple organs, mutations result in identifiable phenotypes only in auditory or ocular sensory organs. The pirouette (pi) mouse also exhibits deafness and an inner ear pathology resembling that of Myo15 mutant mice and thus may be functionally related to Myo15.

Mutation of the novel gene Tmie results in sensory cell defects in the inner ear of spinner, a mouse model of human hearing loss DFNB6.

The recessive mutation at the mouse spinner (sr) locus results in hearing loss and vestibular dysfunction due to neuroepithelial defects in the inner ear. Using a positional cloning strategy, we have identified the mutant locus responsible for this pathology. The affected gene (Tmie) lies within a 40 kb deletion in the original sr allele.