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Bo Chang, Bernard FitzMaurice, Jieping Wang, Patsy M Nishina; A new mouse model of a late onset retinal degeneration (rd21). Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2881.
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© ARVO (1962-2015); The Authors (2016-present)
Mouse models of inherited retinal degeneration are powerful tools to investigate the etiology of similar ocular diseases in humans. We have identified a new retinal degeneration model by routine screening of mouse strains through the Eye Mutant Resource program at The Jackson Laboratory. The aim of this study is to characterize the genetics and disease phenotype of this new model, retinal degeneration 21 (rd21) with a late, but rapidly progressive photoreceptor degeneration that is associated with retinal detachment.
We characterized the clinical effects of this mutation using the Micron III in vivo bright field retinal imaging microscope with image-guided Optical Coherence Tomography (OCT), serial electroretinography (ERG) and histology, and performed genetic linkage analysis to identify the chromosomal location of the mutation.
Mice homozygous for rd21 exhibit attenuated retinal vessels at five month of age and areas of depigmentation at six months of age. Histology and OCT at 5 months of age showed ~20-30% photoreceptor loss, with rapid progressive loss thereafter. By 7 months of age, there are no photoreceptors left and retinal detachment is observed by OCT. Electroretinograms (ERG) of rd21/rd21 mice show near normal Rod ERG responses at 4 months of age, abnormal rod ERG responses (lower ERG a-wave, but near normal b-wave) at five month of age, with normal cone ERG responses within the same time frame. At 8 months of age, neither cone or rod ERGs waveforms are detectable. The inheritance pattern of the rd21 mutation is autosomal recessive. Linkage studies indicated that this new mutation maps to mouse Chromosome 19, with close linkage to a microsatellite marker, D19Mit61. Examination of candidates within the region, revealed an excellent candidate gene, rod outer segment membrane protein 1 (Rom1). Two other candidates mapping within the critical region are Best1 (bestrophin 1) and Stx3 (syntaxin 3).
Late onset and rapidly progressive retinal function loss and degeneration combined with our genetic data suggest that this is a new spontaneous mutation not previously described in mouse. rd21 provides a novel mouse model for late onset photoreceptor degeneration associated with retinal detachment.
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