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R. Gockeln, S. Lindemann, K. Kamino, H. Hedrich, R. Winter, W. Löscher; Retinitis Pigmentosa in Spontaneous Rat Mutants With Sensorineural Deafness and Vestibular Dysfunction – A Rodent Model for Usher Syndrome Phenotype 1 . Invest. Ophthalmol. Vis. Sci. 2003;44(13):1861.
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Purpose: Usher syndromes (USH) are a group of clinically variable diseases with autosomal recessive inheritance, congenital sensorineural hearing loss, vestibular dysfunction and the development of retinitis pigmentosa. The cause of the pathology in USH is unknown and no animal models with the complete phenotype have been available for investigate. We report a rat model of USH phenotype 1, LEW/Ztm-ci2 (ci2). Ci2 homozygotes exhibit circling, hyperactivity, ataxia, a complete sensorineural hearing loss and vestibular defects in the first few postnatal weeks. In view of the clinical findings of USH1-affected patients as well as on the similarities between the phenotype of the ci2 rat mutant and the shaker-1 (sh1) mouse mutant, the present study evaluated the retinal function and morphology of the ci2 mutants. Methods: Electroretinograms (ERGs) were recorded from 12 age- and sex-matched homozygous ci2 +/+ and 10 heterozygous ci2 +/- animals. In addition, age- and sex-matched non-affected LEW/Ztm (previously termed LEW/Han) rats (wt) were used as controls. At the onset of the present experiments, the animals had an age of three to 12 months. The ERG protocols included flash and flicker stimuli under scotopic and photopic conditions. Retinal morphology was observed in rats of comparable age. Results: Light-evoked retinal responses of ci2 mutants demonstrated initial attenuation of scotopic and photopic a- and b-waves compared to the wt. In adult rat mutants at PW40 the scotopic and photopic electroretinogram showed remainder responses or was complete absent, when the wt still had normal ERG responses. Histological examination of the retinal circumference from both eyes showed a complete loss of the outer segments and the outer nuclear layer. In contrast to the retinal circumference, the thickness of the outer segments and the outer nuclear layer of the central retina was decreased, compared to the wt, whereas, retinal pigment epithelium (RPE) did not show any abnormalities. Conclusions: The ci2 rat mutant provides interesting features as an natural model in field of blindness and deafness research and may be useful for studies on syndromic retinal degeneration. Furthermore, the behavioural phenotype of the mutant ci2+/+ makes this animal an interesting model for hyperkinetic movement disorders. The genetic defect in the mutant ci2+/+, thus, leads to the Usher syndrome phenotype 1.
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