Mouse all-cone retina models of Cav1.4 synaptopathy
The voltage-gated calcium channel, Cav1.4 is localized to photoreceptor ribbon synapses and functions both in molecular organization of the synapse and in regulating release of synaptic vesicles. Mutations in Cav1.4 subunits typically present as either incomplete congenital stationary night blindnes...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-04-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnmol.2023.1155955/full |
| _version_ | 1797838587531624448 |
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| author | Joseph G. Laird Ariel Kopel Colten K. Lankford Sheila A. Baker |
| author_facet | Joseph G. Laird Ariel Kopel Colten K. Lankford Sheila A. Baker |
| author_sort | Joseph G. Laird |
| collection | DOAJ |
| description | The voltage-gated calcium channel, Cav1.4 is localized to photoreceptor ribbon synapses and functions both in molecular organization of the synapse and in regulating release of synaptic vesicles. Mutations in Cav1.4 subunits typically present as either incomplete congenital stationary night blindness or a progressive cone-rod dystrophy in humans. We developed a cone-rich mammalian model system to further study how different Cav1.4 mutations affect cones. RPE65 R91W KI; Nrl KO “Conefull” mice were crossed to Cav1.4 α1F or α2δ4 KO mice to generate the “Conefull:α1F KO” and “Conefull:α2δ4 KO” lines. Animals were assessed using a visually guided water maze, electroretinogram (ERG), optical coherence tomography (OCT), and histology. Mice of both sexes and up to six-months of age were used. Conefull: α1F KO mice could not navigate the visually guided water maze, had no b-wave in the ERG, and the developing all-cone outer nuclear layer reorganized into rosettes at the time of eye opening with degeneration progressing to 30% loss by 2-months of age. In comparison, the Conefull: α2δ4 KO mice successfully navigated the visually guided water maze, had a reduced amplitude b-wave ERG, and the development of the all-cone outer nuclear layer appeared normal although progressive degeneration with 10% loss by 2-months of age was observed. In summary, new disease models for studying congenital synaptic diseases due to loss of Cav1.4 function have been created. |
| first_indexed | 2024-04-09T15:44:22Z |
| format | Article |
| id | doaj.art-9732e646ac224baab601a6e84ffe7af6 |
| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-04-09T15:44:22Z |
| publishDate | 2023-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-9732e646ac224baab601a6e84ffe7af62023-04-27T05:25:55ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992023-04-011610.3389/fnmol.2023.11559551155955Mouse all-cone retina models of Cav1.4 synaptopathyJoseph G. LairdAriel KopelColten K. LankfordSheila A. BakerThe voltage-gated calcium channel, Cav1.4 is localized to photoreceptor ribbon synapses and functions both in molecular organization of the synapse and in regulating release of synaptic vesicles. Mutations in Cav1.4 subunits typically present as either incomplete congenital stationary night blindness or a progressive cone-rod dystrophy in humans. We developed a cone-rich mammalian model system to further study how different Cav1.4 mutations affect cones. RPE65 R91W KI; Nrl KO “Conefull” mice were crossed to Cav1.4 α1F or α2δ4 KO mice to generate the “Conefull:α1F KO” and “Conefull:α2δ4 KO” lines. Animals were assessed using a visually guided water maze, electroretinogram (ERG), optical coherence tomography (OCT), and histology. Mice of both sexes and up to six-months of age were used. Conefull: α1F KO mice could not navigate the visually guided water maze, had no b-wave in the ERG, and the developing all-cone outer nuclear layer reorganized into rosettes at the time of eye opening with degeneration progressing to 30% loss by 2-months of age. In comparison, the Conefull: α2δ4 KO mice successfully navigated the visually guided water maze, had a reduced amplitude b-wave ERG, and the development of the all-cone outer nuclear layer appeared normal although progressive degeneration with 10% loss by 2-months of age was observed. In summary, new disease models for studying congenital synaptic diseases due to loss of Cav1.4 function have been created.https://www.frontiersin.org/articles/10.3389/fnmol.2023.1155955/fullconevoltage-gated calcium channelCav1.4α1Fα2δ4CACNA1F |
| spellingShingle | Joseph G. Laird Ariel Kopel Colten K. Lankford Sheila A. Baker Mouse all-cone retina models of Cav1.4 synaptopathy Frontiers in Molecular Neuroscience cone voltage-gated calcium channel Cav1.4 α1F α2δ4 CACNA1F |
| title | Mouse all-cone retina models of Cav1.4 synaptopathy |
| title_full | Mouse all-cone retina models of Cav1.4 synaptopathy |
| title_fullStr | Mouse all-cone retina models of Cav1.4 synaptopathy |
| title_full_unstemmed | Mouse all-cone retina models of Cav1.4 synaptopathy |
| title_short | Mouse all-cone retina models of Cav1.4 synaptopathy |
| title_sort | mouse all cone retina models of cav1 4 synaptopathy |
| topic | cone voltage-gated calcium channel Cav1.4 α1F α2δ4 CACNA1F |
| url | https://www.frontiersin.org/articles/10.3389/fnmol.2023.1155955/full |
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