Abstract
The transgenic P23H line 1 (P23H-1) rat expresses a variant of rhodopsin with a mutation that leads to loss of visual function. This rat strain is an experimental model usually employed to study photoreceptor degeneration. Although the mutated protein should not interfere with other sensory functions, observing severe loss of auditory reflexes in response to natural sounds led us to study auditory brain response (ABR) recording. Animals were separated into different hearing levels following the response to natural stimuli (hand clapping and kissing sounds). Of all the analyzed animals, 25.9% presented auditory loss before 50 days of age (P50) and 45% were totally deaf by P200. ABR recordings showed that all the rats had a higher hearing threshold than the control Sprague-Dawley (SD) rats, which was also higher than any other rat strains. The integrity of the central and peripheral auditory pathway was analyzed by histology and immunocytochemistry. In the cochlear nucleus (CN), statistical differences were found between SD and P23H-1 rats in VGluT1 distribution, but none were found when labeling all the CN synapses with anti-Syntaxin. This finding suggests anatomical and/or molecular abnormalities in the auditory downstream pathway. The inner ear of the hypoacusic P23H-1 rats showed several anatomical defects, including loss and disruption of hair cells and spiral ganglion neurons. All these results can explain, at least in part, how hearing impairment can occur in a high percentage of P23H-1 rats. P23H-1 rats may be considered an experimental model with visual and auditory dysfunctions in future research.
Highlights
The P23H mutant rhodopsin transgenic rat is an experimental model of retinal degeneration that exhibits gradual, fast photoreceptor loss with similar properties to human autosomal dominant retinitis pigmentosa (Berson et al, 1991; Lewin et al, 1998)
While all the SD rats responded to the single clap (SC) and kissing sounds (KS), not all the P23H rats responded to these stimuli
We found that most rats responded to both the KS and SC (Level I), some responded to only one stimuli and displayed slow alert movements (Level II), while others did not respond to any sound (Level III), even at P20 (Table 1)
Summary
The P23H mutant rhodopsin transgenic rat is an experimental model of retinal degeneration that exhibits gradual, fast photoreceptor loss with similar properties to human autosomal dominant retinitis pigmentosa (Berson et al, 1991; Lewin et al, 1998). There are three P23H mutant rat lines with different photoreceptor degeneration rates (http:// www.ucsfeye.net/mlavailRDratmodels.shtml). The Line 1 animals have a higher level of transgene expression than the Line 3 animals and they have faster degeneration than the rats of Lines 2 and 3. Homozygous animals produce a faster degeneration rate than heterozygotes; the retina of these animals has been studied in depth, but the rest of the central and peripheral nervous systems remains completely unexplored. We evaluate the auditory capacity of the homozygous P23H line 1 (P23H-1) rats at different ages by using physiological and morphological techniques. Rhodopsins virally targeted within auditory neurons of the dorsal cochlear nucleus had no detrimental effects on hearing and may be useful to modulate the activity of specific auditory neurons (Shimano et al, 2013)
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