Organ of Corti surface preparations from A/J and B6 mice at two months of age. Photomicrographs of the organ of Corti from the mid-basal and mid-apical turns of 9 week old A/J (C and D) and B6 mice (A and B). Magnification is 1000X.

Cross sections (3 μm) taken through the habenula perforata at mid-basal turn (represents 2–4 kHz) showing the nerve fiber density in a 9-week- and a 5-month-old A/J (A, B) and B6 mouse (C, D) respectively (1000X magnification). Nerve fiber density in habenular openings of A/J mice was similar to the density in B6 mice of the same age.

Cytocochleograms showing the percentage of OHC and IHC loss in typical A/J mice at 9 weeks (B) and 20 weeks (D) of age and B6 mice at 9 weeks (A) and 20 weeks (C) of age. Vertical bars show the frequency-to-place map for the 8, 16 and 32 kHz test tones (Ehret, 1975).

Cross sections (3 μm) through the modiolus of cochleae from a 9-week-old A/J (A) and B6 (B)mouse. Hair cells were missing in the A/J mouse, but present in the B6 mouse. The density of SGN in the A/J mouse was similar to that in the B6 mouse (400X). Cross sections (3 μm) through Rosenthal’s canal at mid-basal turn (represents 2–4 kHz) shown in 5-month-old A/J (C) and B6 (D) mice; 1000X magnification. The density and gross appearance of the SGN in the A/J cochlea were similar to the B6 cochlea.

The most likely position of ahl4 on mouse Chr 10 as determined from the (A/J x CAST) x A/J backcross. LOD scores for the associations of DNA markers with 16 kHz ABR thresholds of three-month-old N2 mice. To control for the epistatic effect of the ahl locus, only the subset of backcross mice that were homozygous for the A/J-derived allele at the D10Mit138 locus were evaluated (74 mice). Backcross mice heterozygous for A/J and CAST-derived alleles of D10Mit138 exhibited normal thresholds and so were not included in this analysis.

(A) Scatter plots showing the percentage of OHC missing as a function of age at locations 0–25%, 25–50%, 50–75% and 75–100% distance from the apex of the cochlea. Boltzmann sigmoidal function fit to the data (GraphPad Prism 5). Left column and right columns display data for A/J and B6 mice respectively. Filled circles show data from individual animals in the current study. Open squares in right column plots show mean (n=10) data from B6 mice from Spongr et al. (1998). (B) Scatterplots for the percentage of IHC missing as in Figure 8A.

ABR threshold variation among 14 AXB and 13 BXA recombinant inbred (RI) strains tested between 6 and 9 months of age. Means and standard error bars for 16 kHz thresholds and the numbers of mice tested (in parentheses) are shown for each strain. At this age, average thresholds of parental strain A/J mice are greater than 90 dB, whereas those of B6 mice are less than 40 dB. A statistically significant association of ABR thresholds was found with loci on distal Chr 10 (max LOD 4.3).

The effects of the ahl and ahl4 loci on ABR thresholds of (A/J x CAST/Ei) x A/J backcross mice. Each bar represents the mean 16 kHz ABR threshold (with its associated standard error) for a given genotype class tested at 3 and 6 months of age. Black bars represent mice with D10Mit138 AA genotypes, and gray bars represent mice with D10Mit138 AC genotypes, where A is the A/J-derived allele and C is the CAST/Ei-derived allele.
A) The ahl locus (marked by D10Mit138) has a highly significant effect on ABR thresholds of (A/J x CAST) x A/J backcross mice. All 180 backcross mice were analyzed for D10Mit138 genotypes (AC, heterozygous for A/J and CAST alleles; AA, homozygous for A/J allele). Note that only mice with an AA genotype at D10Mit138 exhibit elevated thresholds at the ages tested.
B) The ahl4 locus (marked by D10Mit103) has a marked effect on ABR thresholds, but only in backcross mice that are homozygous for the A/J-derived allele at the ahl locus (D10Mit138 AA genotypes). Means and standard error bars for 16 kHz ABR thresholds of N2 backcross mice tested at 3 and 6 months of age. Only the 74 mice that were homozygous for the A/J-derived allele at the D10Mit138 locus were analyzed for threshold associations with D10Mit103 genotypes (AC, heterozygous for A/J and CAST alleles; AA, homozygous for A/J allele). C) The ahl4 locus (marked by D10Mit103) has no effect on ABR thresholds in backcross mice that are heterozygous at the ahl locus (D10Mit138 AC genotypes).

A) ABR threshold variation among 21 B6.A chromosome substitution strains tested between 5 and 7 months of age. Means and standard error bars for 16 kHz thresholds are shown for each strain. A minimum of 8 mice were tested per strain. Note that Chr 10 appears to be the largest contributor to the increased hearing loss of A/J mice relative to B6 mice.
B) The effect of an A/J-derived Chr 10 (containing ahl4) on ABR thresholds of mice with an otherwise B6 genome. Means and standard error bars for 16 kHz ABR thresholds of B6 mice are compared with those of age-matched mice from the B6.A-Chr10 strain. Four or five mice from each strain were tested at each timepoint.

ABR thresholds of A/J and B6 mice. ABR thresholds (dB SPL=sound pressure level in decibels) of A/J and B6 mice were determined for the four stimuli shown on the X-axis. Each data point represents an average threshold value (calculated as the arithmetic mean) for each age group (n=6 mice) described in the adjacent data point legend. Error bars indicate the standard deviation from the mean, shown only in the positive direction for simplicity. Rectangles ranging from 0 to a positive value delineate the range of threshold values empirically determined to fall within a normal hearing range (Zheng et al., 1999). All points lying outside the rectangles are considered to be hearing impaired.