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W. Baehr, J.M. Frederick, T. Doan, F. Rieke, P. Detwiler, H. Zhang; The Physiological Role of PDE in Mouse Photoreceptors . Invest. Ophthalmol. Vis. Sci. 2005;46(13):1699.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To identify the function of PDEΔ, a prenyl binding protein originally copurified with rod cGMP phosphodiesterase (PDE), in photoreceptors. Methods: Establishment of a PDEΔ knockout (PDEΔ–/–) mouse, immunoblotting, immunocytochemistry, electroretinography, single cell recordings. Results: We showed previously that PDEΔ specifically interacts with isoprenyl side chains suggesting a role as a universal prenyl binding protein. To identify the physiological role of PDEΔ, we first established a mouse line in which the PDEΔ gene is floxed (LoxP sites flanking exons 2 and 4). When the floxPDEΔ+/+ line is bred to a mouse expressing Cre recombinase under the control of the CMV promoter, a PDEΔ–/– mouse can be established in which exons 2–4 of the PDEΔ gene are deleted. We found that mice with germline deletion of PDEΔ are viable suggesting that PDEΔ is not essential for development and viability. Retinas of PDEΔ–/– mice have slightly shorter ONL thickness at age 3 months. Immunocytochemistry with a GRK1–specific monoclonal antibody shows that GRK1 levels in PDEΔ–/– cones are undetectable while GRK1 levels in PDEΔ–/– rods are approximately 20% of wild–type. Paired–flash ERGs with ISIs ranging form 500 msec to 5 sec show defects in rod and cone recovery. Blood vessels are present in the subretinal space of 1 year old PDEΔ–/– mouse retinas. This was confirmed for rods in single cell recordings, which showed that time–to–peak, integration time and time for half recovery of the mean dim flash response was increased in the PDEΔ–/– mice by 40, 145 and 80 % respectively relative to wild type. Conclusions: We conclude that PDEΔ is involved in transport of farnesylated GRK1 to photoreceptor outer segments in the mouse retina. Since humans, but not mice, express GRK7 (which is geranylgeranylated interacting much more weakly with PDEΔ) in cones, a possible human phenotype with PDEΔ loss of function may resemble congenital stationary night blindness affecting only rods. The PDEΔ–/– mouse is a potential animal model for studying wet–form AMD (Age–related macular degeneration), which involves neovascularization.
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