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Stylianos Michalakis, Heidi Geiger, Silke Haverkamp, Franz Hofmann, Andrea Gerstner, Martin Biel; Impaired Opsin Targeting and Cone Photoreceptor Migration in the Retina of Mice Lacking the Cyclic Nucleotide-Gated Channel CNGA3. Invest. Ophthalmol. Vis. Sci. 2005;46(4):1516-1524. doi: 10.1167/iovs.04-1503.
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© 2015 Association for Research in Vision and Ophthalmology.
purpose. To characterize molecular and cellular changes in the mouse retina caused by the genetic deletion of the cone cyclic nucleotide-gated channel (CNG) subunit CNGA3.
methods. Retinas of wild-type and CNGA3-deficient (CNGA3−/−) mice from 9 days up to 22 months of age were analyzed by immunohistochemistry, electron microscopy, and molecular biological methods.
results. CNGA3−/− cones failed to transport opsins into outer segments, downregulated various proteins of the phototransduction cascade, and induced apoptotic death. Loss of CNGA3 did not affect the transcription of cone-specific genes. Cone degeneration was evident from the second postnatal week on, and it proceeded significantly faster in the ventral than in the dorsal part of the retina. Ventral cones were completely missing after the third postnatal month, whereas residual dorsal cones were present, even in 22-month-old knockout mice. CNGA3−/− cone somata exhibited profoundly delayed migration during postnatal development. At the time of eye opening, most CNGA3−/− cones had displaced somata localized close to or in the outer plexiform layer. These cones lacked the characteristic synaptic pedicle, but revealed synapselike contacts to second-order neurons at their somata. At later stages, most of the surviving CNGA3−/− cones had correctly located somata and morphologically normal synapses.
conclusions. The loss of CNGA3 impairs the targeting of cone opsins and the expression of other visual cascade proteins. In addition, CNGA3 appears to be essential for normal postnatal migration of cone somata. After loss of cone outer segment proteins, CNGA3−/− cones induce apoptotic cell death.
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