Quantitative trait loci on chromosome 5 for susceptibility to frequency-specific effects on hearing in DBA/2J mice

The DBA/2J strain is a model for early-onset, progressive hearing loss in humans, asconfirmed in the present study. DBA/2J mice showed progression of hearing loss tolow-frequency sounds from ultrasonic-frequency sounds and profound hearing loss at allfrequencies before 7 months of age. It is known that the early-onset hearing loss ofDBA/2J mice is caused by affects in the ahl(Cdh23^ahl) and ahl8(Fscn2^ahl8) alleles of the cadherin 23 and fascin 2 genes,respectively. Although the strong contributions of theFscn2^ahl8 allele were detected in hearing loss at 8- and16-kHz stimuli with LOD scores of 5.02 at 8 kHz and 8.84 at 16 kHz, hearing loss effectswere also demonstrated for three new quantitative trait loci (QTLs) for the intervals of50.3–54.5, 64.6–119.9, and 119.9–137.0 Mb, respectively, on chromosome 5, with significantLOD scores of 2.80–3.91 for specific high-frequency hearing loss at 16 kHz by quantitativetrait loci linkage mapping using a (DBA/2J × C57BL/6J) F₁ × DBA/2J backcrossmice. Moreover, we showed that the contribution of Fscn2^ahl8to early-onset hearing loss with 32-kHz stimuli is extremely low and raised thepossibility of effects from the Cdh23^ahl allele and anotherdominant quantitative trait locus (loci) for hearing loss at this ultrasonic frequency.Therefore, our results suggested that frequency-specific QTLs control early-onset hearingloss in DBA/2J mice.