title: Overexpression of retinal degeneration slow (RDS) protein adversely affects rods in the rd7 model of enhanced S-cone syndrome.
abstract: The nuclear receptor NR2E3 promotes expression of rod photoreceptor genes while repressing cone genes. Mice lacking NR2E3 (Nr2e3(rd7/rd7) referred to here as rd7) are a model for enhanced S-cone syndrome, a disease associated with increased sensitivity to blue light and night blindness. Rd7 retinas have reduced levels of the outer segment (OS) structural protein retinal degeneration slow (RDS). We test the hypothesis that increasing RDS levels would improve the Rd7 phenotype. Transgenic mice over-expressing normal mouse peripherin/RDS (NMP) in rods and cones were crossed onto the rd7 background. Disease phenotypes were assessed in NMP/rd7 eyes and compared to wild-type (WT) and rd7 eyes at postnatal day 30. NMP/rd7 retinas expressed total RDS (transgenic and endogenous) message at WT levels, and NMP protein was correctly localized to the OS. NMP/rd7 retinas have shorter OSs compared to rd7 and WT and significantly reduced number of rosettes. NMP/rd7 mice also exhibited significant deficits in scotopic ERG amplitudes compared to rd7 while photopic amplitudes remained unaffected. Protein levels of rhodopsin, RDS, and the RDS homologue ROM-1 were significantly reduced in the NMP/rd7 retinas compared to rd7. We show that correcting the levels of RDS gene expression does not improve the phenotype of the rd7 suggesting that RDS deficiency is not responsible for the defect in this model. We suggest that the specific rod defect in the NMP/rd7 is likely associated with ongoing problems in the rd7 that are related to the expression of cone genes in rod cells, a characteristic of the model.
authors: Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America.
authors: Dibyendu
authors: D
authors: Chakraborty
authors: Shannon M
authors: SM
authors: Conley
authors: Muna I
authors: MI
authors: Naash
mesh_terms: D000200:Action Potentials; D000818:Animals; D015785:Eye Diseases, Hereditary / Q000378:metabolism / Q000473:pathology*; D015870:Gene Expression; D051379:Mice; D008822:Mice, Transgenic; D064531:Peripherins / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D055503:Protein Multimerization; D012160:Retina / Q000473:pathology; D017949:Retinal Cone Photoreceptor Cells / Q000502:physiology; D012162:Retinal Degeneration / Q000378:metabolism / Q000473:pathology*; D055214:Retinal Photoreceptor Cell Outer Segment / Q000378:metabolism / Q000473:pathology; D017948:Retinal Rod Photoreceptor Cells / Q000378:metabolism*; D014786:Vision Disorders / Q000378:metabolism / Q000473:pathology*
chemical_list: D064531:Peripherins; C578996:Prph2 protein, mouse
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