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O Dick, S tom Dieck, W Altrock, J Ammermüller, ED Gundelfinger, JH Brandstatter; A Mutation In The Gene For The Presynaptic Cytomatrix Protein Bassoon Prevents The Development Of Photoreceptor Ribbon Synapses . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2693.
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Purpose:The cytomatrix protein Bassoon is thought to be involved in both the organization and the function of the presynaptic active zone at synapses. In the mammalian retina, Bassoon is expressed at photoreceptor ribbon synapses and at conventional GABAergic and glycinergic synapses (Dick et al., 2001, J. Comp. Neurol. 439: 224-234). To find out more about the function of Bassoon, we studied a mouse mutant that lacks the central exons of the bassoon gene. Methods:Using immunocytochemistry, we labeled certain populations of neurons in retinal sections of adult Bsn mutant and wild-type mice, and examined them by light microscopy. The ultrastructural appearance of photoreceptor synapses of mutant and wild-type retinae was examined at different postnatal stages up to adulthood by electron microscopy. ERG recordings of wild-type and mutant retinae were performed. Results:We found dramatic changes in the dendritic branching patterns of horizontal and rod bipolar cells but not of cone bipolar cells in the Bsn mutant retina. Processes of horizontal cells and dendrites of rod bipolar cells in the mutant retina extended far beyond the outer plexiform layer into the outer nuclear layer. The developmental study showed that in the mutant retina most of the photoreceptor terminals lacked synaptic ribbons at all postnatal stages examined. When ribbons were found, they were detached from the plasma membrane at the synaptic site and floated freely in the cytoplasm of the photoreceptor terminals. Scotopic ERG recordings from dark-adapted mice showed no differences in the a-wave of the ERG between wild-type and mutant mice but a significantly smaller amplitude of the b-wave in the mutant. Conclusion:Bassoon is essential for the development and the structural integrity of the photoreceptor ribbon synapses. Loss of Bassoon prevents photoreceptor ribbon synapse formation, leading to impaired photoreceptor signaling and dramatic structural alterations in the outer retina of the Bsn mutant mouse.
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