PMC:548520 / 24978-28070 JSONTXT

{"project":"2_test","denotations":[{"id":"15676071-6715580-12933302","span":{"begin":236,"end":238},"obj":"6715580"},{"id":"15676071-15161873-12933303","span":{"begin":410,"end":412},"obj":"15161873"},{"id":"15676071-6055897-12933304","span":{"begin":1061,"end":1063},"obj":"6055897"},{"id":"15676071-563768-12933305","span":{"begin":1064,"end":1066},"obj":"563768"},{"id":"15676071-11733058-12933306","span":{"begin":1841,"end":1843},"obj":"11733058"},{"id":"15676071-10329014-12933307","span":{"begin":2532,"end":2534},"obj":"10329014"}],"text":"The Crx-/- mouse demonstrates the most severe abnormality of photoreceptor synapses reported to date. The peripherin-/- mouse develops a normal complement of photoreceptor terminals which then degenerate as the photoreceptors are lost [30]. Also, similarly in rhodopsin (Rho) and cyclic nucleotide-gated channel, alpha-3 (CNGA3) double knockout mice (Rho-/-, CNGA3-/-), synapses are reported to form normally [49]. These observations demonstrate that photoreceptor synaptogenesis can occur in the absence of outer segment formation. In keeping with this observation is the fact that some electroretinogram activity is present in peripherin-/- mice, suggesting that minimal phototransduction is present in these mice, enough to drive activity at the photoreceptor synapse. In vitro studies wherein synapse elements are formed in the absence of proper outer segment development and, therefore, possible absence of light-dependent photoreceptor activity, have indicated the independence of phototransduction and synapse formation, at least for the initial stages [50,51]. These data then suggest that the fact that the Crx-/- photoreceptors do not have proper synaptic endings is not due to a lack of outer segment formation. A more likely explanation is that Crx plays a role in photoreceptor synapse formation, perhaps by regulating directly, or indirectly, important genes in this process. Using immunohistochemistry, we examined the expression of common pre-synaptic terminal proteins, including KIF3a, SV2, and synaptophysin, and were unable to observe qualitative differences between Crx-/- and control tissue at P14 (data not shown). Examination of their RNA levels by SAGE showed no significant difference for all 3 genes, though very few tags were recovered from these genes and thus the analysis of RNA levels may not be significant [35]. However, since other genes expressed in photoreceptors were significantly altered in their expression level in the Crx-/- mouse, there are many candidates that could be important for photoreceptor morphogenesis. Tags from three genes from proteins expressed in photoreceptor terminals were found to be decreased in a statistically significant fashion, namely the HGF-regulated tyrosine kinase substrate, the CRIPT protein, and synaptotagmin 1 (Blackshaw and Cepko, unpublished data). An example of a gene that was increased in the Crx-/- retina is HRG4 (a homologue of the C. elegans Unc119 gene) (Blackshaw and Cepko, unpublished data) which encodes a component of the ribbon synapse [33]. The fact that it is upregulated might indicate a response to the lack of proper terminal structures. Several other genes encoding putative cytoskeletal elements also were increased (e.g. microtubule associated protein 4) or decreased (e.g. cofilin 1) in the Crx-/- retina, with P values of \u003c.005. It is not known whether any of these genes are involved in building or regulating synaptic structures, but they are now genes that might lead to a better understanding of the construction and function of the relatively unique structure of the ribbon synapse."}

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Crx-/- mouse demonstrates the most severe abnormality of photoreceptor synapses reported to date. The peripherin-/- mouse develops a normal complement of photoreceptor terminals which then degenerate as the photoreceptors are lost [30]. Also, similarly in rhodopsin (Rho) and cyclic nucleotide-gated channel, alpha-3 (CNGA3) double knockout mice (Rho-/-, CNGA3-/-), synapses are reported to form normally [49]. These observations demonstrate that photoreceptor synaptogenesis can occur in the absence of outer segment formation. In keeping with this observation is the fact that some electroretinogram activity is present in peripherin-/- mice, suggesting that minimal phototransduction is present in these mice, enough to drive activity at the photoreceptor synapse. In vitro studies wherein synapse elements are formed in the absence of proper outer segment development and, therefore, possible absence of light-dependent photoreceptor activity, have indicated the independence of phototransduction and synapse formation, at least for the initial stages [50,51]. These data then suggest that the fact that the Crx-/- photoreceptors do not have proper synaptic endings is not due to a lack of outer segment formation. A more likely explanation is that Crx plays a role in photoreceptor synapse formation, perhaps by regulating directly, or indirectly, important genes in this process. Using immunohistochemistry, we examined the expression of common pre-synaptic terminal proteins, including KIF3a, SV2, and synaptophysin, and were unable to observe qualitative differences between Crx-/- and control tissue at P14 (data not shown). Examination of their RNA levels by SAGE showed no significant difference for all 3 genes, though very few tags were recovered from these genes and thus the analysis of RNA levels may not be significant [35]. However, since other genes expressed in photoreceptors were significantly altered in their expression level in the Crx-/- mouse, there are many candidates that could be important for photoreceptor morphogenesis. Tags from three genes from proteins expressed in photoreceptor terminals were found to be decreased in a statistically significant fashion, namely the HGF-regulated tyrosine kinase substrate, the CRIPT protein, and synaptotagmin 1 (Blackshaw and Cepko, unpublished data). An example of a gene that was increased in the Crx-/- retina is HRG4 (a homologue of the C. elegans Unc119 gene) (Blackshaw and Cepko, unpublished data) which encodes a component of the ribbon synapse [33]. The fact that it is upregulated might indicate a response to the lack of proper terminal structures. Several other genes encoding putative cytoskeletal elements also were increased (e.g. microtubule associated protein 4) or decreased (e.g. cofilin 1) in the Crx-/- retina, with P values of \u003c.005. It is not known whether any of these genes are involved in building or regulating synaptic structures, but they are now genes that might lead to a better understanding of the construction and function of the relatively unique structure of the ribbon synapse."}

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Crx-/- mouse demonstrates the most severe abnormality of photoreceptor synapses reported to date. The peripherin-/- mouse develops a normal complement of photoreceptor terminals which then degenerate as the photoreceptors are lost [30]. Also, similarly in rhodopsin (Rho) and cyclic nucleotide-gated channel, alpha-3 (CNGA3) double knockout mice (Rho-/-, CNGA3-/-), synapses are reported to form normally [49]. These observations demonstrate that photoreceptor synaptogenesis can occur in the absence of outer segment formation. In keeping with this observation is the fact that some electroretinogram activity is present in peripherin-/- mice, suggesting that minimal phototransduction is present in these mice, enough to drive activity at the photoreceptor synapse. In vitro studies wherein synapse elements are formed in the absence of proper outer segment development and, therefore, possible absence of light-dependent photoreceptor activity, have indicated the independence of phototransduction and synapse formation, at least for the initial stages [50,51]. These data then suggest that the fact that the Crx-/- photoreceptors do not have proper synaptic endings is not due to a lack of outer segment formation. A more likely explanation is that Crx plays a role in photoreceptor synapse formation, perhaps by regulating directly, or indirectly, important genes in this process. Using immunohistochemistry, we examined the expression of common pre-synaptic terminal proteins, including KIF3a, SV2, and synaptophysin, and were unable to observe qualitative differences between Crx-/- and control tissue at P14 (data not shown). Examination of their RNA levels by SAGE showed no significant difference for all 3 genes, though very few tags were recovered from these genes and thus the analysis of RNA levels may not be significant [35]. However, since other genes expressed in photoreceptors were significantly altered in their expression level in the Crx-/- mouse, there are many candidates that could be important for photoreceptor morphogenesis. Tags from three genes from proteins expressed in photoreceptor terminals were found to be decreased in a statistically significant fashion, namely the HGF-regulated tyrosine kinase substrate, the CRIPT protein, and synaptotagmin 1 (Blackshaw and Cepko, unpublished data). An example of a gene that was increased in the Crx-/- retina is HRG4 (a homologue of the C. elegans Unc119 gene) (Blackshaw and Cepko, unpublished data) which encodes a component of the ribbon synapse [33]. The fact that it is upregulated might indicate a response to the lack of proper terminal structures. Several other genes encoding putative cytoskeletal elements also were increased (e.g. microtubule associated protein 4) or decreased (e.g. cofilin 1) in the Crx-/- retina, with P values of \u003c.005. It is not known whether any of these genes are involved in building or regulating synaptic structures, but they are now genes that might lead to a better understanding of the construction and function of the relatively unique structure of the ribbon synapse."}

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Crx-/- mouse demonstrates the most severe abnormality of photoreceptor synapses reported to date. The peripherin-/- mouse develops a normal complement of photoreceptor terminals which then degenerate as the photoreceptors are lost [30]. Also, similarly in rhodopsin (Rho) and cyclic nucleotide-gated channel, alpha-3 (CNGA3) double knockout mice (Rho-/-, CNGA3-/-), synapses are reported to form normally [49]. These observations demonstrate that photoreceptor synaptogenesis can occur in the absence of outer segment formation. In keeping with this observation is the fact that some electroretinogram activity is present in peripherin-/- mice, suggesting that minimal phototransduction is present in these mice, enough to drive activity at the photoreceptor synapse. In vitro studies wherein synapse elements are formed in the absence of proper outer segment development and, therefore, possible absence of light-dependent photoreceptor activity, have indicated the independence of phototransduction and synapse formation, at least for the initial stages [50,51]. These data then suggest that the fact that the Crx-/- photoreceptors do not have proper synaptic endings is not due to a lack of outer segment formation. A more likely explanation is that Crx plays a role in photoreceptor synapse formation, perhaps by regulating directly, or indirectly, important genes in this process. Using immunohistochemistry, we examined the expression of common pre-synaptic terminal proteins, including KIF3a, SV2, and synaptophysin, and were unable to observe qualitative differences between Crx-/- and control tissue at P14 (data not shown). Examination of their RNA levels by SAGE showed no significant difference for all 3 genes, though very few tags were recovered from these genes and thus the analysis of RNA levels may not be significant [35]. However, since other genes expressed in photoreceptors were significantly altered in their expression level in the Crx-/- mouse, there are many candidates that could be important for photoreceptor morphogenesis. Tags from three genes from proteins expressed in photoreceptor terminals were found to be decreased in a statistically significant fashion, namely the HGF-regulated tyrosine kinase substrate, the CRIPT protein, and synaptotagmin 1 (Blackshaw and Cepko, unpublished data). An example of a gene that was increased in the Crx-/- retina is HRG4 (a homologue of the C. elegans Unc119 gene) (Blackshaw and Cepko, unpublished data) which encodes a component of the ribbon synapse [33]. The fact that it is upregulated might indicate a response to the lack of proper terminal structures. Several other genes encoding putative cytoskeletal elements also were increased (e.g. microtubule associated protein 4) or decreased (e.g. cofilin 1) in the Crx-/- retina, with P values of \u003c.005. It is not known whether any of these genes are involved in building or regulating synaptic structures, but they are now genes that might lead to a better understanding of the construction and function of the relatively unique structure of the ribbon synapse."}