Genome-wide linkage analyses identify Hfhl1 and Hfhl3 with frequency-specific effects on the hearing spectrum of NIH Swiss mice.

Background: The mammalian cochlea receives and analyzes sound at specific places along the cochlea coil, commonly referred to as the tonotopic map. Although much is known about the cell-level molecular defects responsible for severe hearing loss, the genetics responsible for less severe and frequency-specific hearing loss remains unclear. We recently identified quantitative trait loci (QTLs) Hfhl1 and Hfhl2 that affect high-frequency hearing loss in NIH Swiss mice.

High-frequency sensorineural hearing loss and its underlying genetics (Hfhl1 and Hfhl2) in NIH Swiss mice.

Studies using inbred strains of mice have been invaluable for identifying alleles that adversely affect hearing. However, the efficacy of those studies is limited by the phenotypes that these strains express and the alleles that they segregate. Here, by selectively breeding phenotypically and genetically heterogeneous NIH Swiss mice, we generated two lines-the all-frequency hearing loss (AFHL) line and the high-frequency hearing loss (HFHL) line-with differential hearing loss.

Gipc3 mutations associated with audiogenic seizures and sensorineural hearing loss in mouse and human.

Sensorineural hearing loss affects the quality of life and communication of millions of people, but the underlying molecular mechanisms remain elusive. Here, we identify mutations in Gipc3 underlying progressive sensorineural hearing loss (age-related hearing loss 5, ahl5) and audiogenic seizures (juvenile audiogenic monogenic seizure 1, jams1) in mice and autosomal recessive deafness DFNB15 and DFNB95 in humans. Gipc3 localizes to inner ear sensory hair cells and spiral ganglion.

The TRPML3 channel: from gene to function.

TRPML3 is a transient receptor potential (TRP) channel that is encoded by the mucolipin 3 gene (MCOLN3), a member of the small mucolipin gene family. Mcoln3 shows a broad expression pattern in embryonic and adult tissues that includes differentiated cells of skin and inner ear. Dominant mutant alleles of murine Mcoln3 cause embryonic lethality, pigmentation defects and deafness.

Polygenic inheritance of sensorineural hearing loss (Snhl2, -3, and -4) and organ of Corti patterning defect in the ALR/LtJ mouse strain.

Progressive sensorineural hearing loss in humans is a common and debilitating impairment. Sensorineural deafness in inbred strains of mice is a similarly common and genetically diverse phenotype providing experimental models to study the underlying genetics and the biological effects of the risk factors. Here, we report that ALR/LtJ mice develop early-onset profound sensorineural hearing loss as evidenced by high-to-low frequency hearing threshold shifts, absent distortion-product otoacoustic emissions, and normal endocochlear potentials.