Mouse all-cone retina models of Cav1.4 synaptopathy

Joseph Laird; Ariel Kopel; Colten Lankford; Sheila Baker

doi:10.3389/fnmol.2023.1155955

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Mouse all-cone retina models of Cav1.4 synaptopathy

Journal article

Open access

Peer reviewed

Mouse all-cone retina models of Cav1.4 synaptopathy

Joseph Laird, Ariel Kopel, Colten Lankford and Sheila Baker

Frontiers in molecular neuroscience, Vol.16, 1155955

04/27/2023

DOI: 10.3389/fnmol.2023.1155955

PMCID: PMC10174292

PMID: 37181655

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https://doi.org/10.3389/fnmol.2023.1155955View

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Abstract

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.

Animal Models

Antibodies

Disease

Mutation

Age

Calcium channels (voltage-gated)

Channel gating

Cones

Degeneration

Dystrophy

Electroretinograms

Laboratory animals

Nyctalopia

Photoreceptors

Retina

Stationary night blindness

Synaptic ribbons

Synaptic vesicles

Details

Title: Subtitle: Mouse all-cone retina models of Cav1.4 synaptopathy
Creators: Joseph Laird
Ariel Kopel
Colten Lankford
Sheila Baker
Resource Type: Journal article
Publication Details: Frontiers in molecular neuroscience, Vol.16, 1155955
DOI: 10.3389/fnmol.2023.1155955
PMID: 37181655
PMCID: PMC10174292
NLM abbreviation: Front Mol Neurosci
eISSN: 1662-5099
Publisher: Frontiers Research Foundation
Grant note: DOI: 10.13039/100000053, name: National Eye Institute, award: R01 EY026817 and R01 EY020542
Language: English
Date published: 04/27/2023
Academic Unit: Iowa Neuroscience Institute; Biochemistry and Molecular Biology; University College Courses; Ophthalmology and Visual Sciences
Record Identifier: 9984400755202771

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