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I. Bicknell, R.M. Darrow, D.T. Organisciak; Evaluation of Hearing in the P23H Rat Model of Retinitis Pigmentosa . Invest. Ophthalmol. Vis. Sci. 2003;44(13):3067.
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Purpose: Some forms of retinitis pitmentosa (RP) are accompanied by auditory deficits, Ushers, Alstrom, and Refsum syndromes, for example. RP in humans carrying the P23H mutation is not associated with hearing abnormalities; however, random insertion of the mutated gene into a rat genome may alter the level of gene expression, influencing the range of tissues affected and/or the degree of effect. In the P23H transgenic rat, retinal degeneration is well documented, but the status of the auditory system is unknown. Detection of auditory dysfunction in the P23H rat would identify a new oculo-auditory syndromic animal model. Methods: The auditory brainstem response (ABR) was used to evaluate the auditory status of male and female P23H homozygotes (line 3). Homozygotes were used because they carry two copies of the transgene and exhibit more severe retinal degeneration. Our rationale was that auditory abnormalities, if present, also would be more severe in homozygotes. Four acoustic stimuli were used to elicit the auditory response: 100µs clicks and 4-, 8-, and 32-kHz tone bursts of 3-ms duration. Stimuli were presented, via pediatric ear inserts, in a descending intensity series beginning at a sound pressure level of 90 dB. Animals were lightly anesthetized and thermoregulated during the ABR procedure. Thresholds, latencies, and amplitudes of Peak II, the last peak to disappear from the ABR waveform with decreasing intensity of the acoustic signal, were compared to ABR parameters obtained from normal Sprague Dawley rats. Results: As expected, whole-eye rhodopsin and photoreceptor DNA levels in the P23H homozygotes were dramatically reduced, by 75% and 60% respectively, compared to normal Sprague-Dawleys. ABR thresholds in P23H transgenic rats were not significantly different from those of normal animals for any of the acoustic stimuli, indicating no evidence for hearing loss. Average Peak II latency for the 32-kHz signal was nearly identical in the two groups, but average amplitude was significantly higher for the P23H rats at intensities of 60 to 90 dB. Analysis of the data on the basis of gender showed slightly higher Peak II amplitude in females than in males, probably reflecting differences in skull thickness. No gender-related differences were noted in latency or thresholds. Conclusions: The P23H rat model of RP has hearing that is as least as good as that of normal Sprague-Dawley rats. Higher Peak II amplitude in the P23H animals suggests greater sensitivity to sound.
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