Photoreceptor degeneration in a new Cacna1f mutant mouse model
| Autor: | Jijing Pang, Bernard FitzMaurice, Bo Chang, Jieping Wang, Xufeng Dai, Shiyi Pang |
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| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Opsin Candidate gene Retinal Disorder Calcium Channels L-Type Genotyping Techniques genetic structures Mutant Biology medicine.disease_cause Polymerase Chain Reaction Article Retina Mice 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound Exon 0302 clinical medicine Electroretinography medicine Animals Frameshift Mutation Night Vision X-linked recessive inheritance Mutation Retinal Degeneration Rod Opsins Retinal Exons Immunohistochemistry Molecular biology Mice Mutant Strains eye diseases Sensory Systems Mice Inbred C57BL Disease Models Animal Ophthalmology 030104 developmental biology chemistry 030221 ophthalmology & optometry Calcium Channels sense organs Polymorphism Restriction Fragment Length Tomography Optical Coherence Photoreceptor Cells Vertebrate |
| Zdroj: | Experimental Eye Research. 179:106-114 |
| ISSN: | 0014-4835 |
| Popis: | The Cacna1f gene encodes the α1F subunit of an L-type voltage-gated calcium channel, Cav1.4. In photoreceptor synaptic terminals, Cav1.4 channels mediate glutamate release and postsynaptic responses associated with visual signal transmission. We have discovered a new Cacna1f mutation in nob9 mice, which display more severe phenotypes than do nob2 mice. To characterize the nob9 phenotype at different ages, we examined the murine fundus, applied retinal optical coherence tomography, measured flash electroretinograms (ERGs) in vivo, and analyzed the retinal histology in vitro. After identifying the X-linked recessive inheritance trait, we sequenced Cacna1f as the candidate gene. Mutations in this gene were detected by polymerase chain reaction (PCR) and confirmed by restriction fragment length polymorphism. Morphologically, an early-onset of retinal disorder was detected, and the degeneration of the outer plexiform layers progressed rapidly. Moreover, the mutant mice showed drastically reduced scotopic ERGs with increasing age. In 14-month-old nob9 retinas, immunostaining of cone opsins demonstrated a reduction in the number of short-wavelength opsins (S-opsins) to 54% of wild-type levels, and almost no middle-wavelength opsins (M-opsins) were observed. No cone ERGs could be detected from residual cones, in which S-opsins abnormally migrated to inner segments of the photoreceptors. The mutations of the Cacna1f gene in nob9 mice involved both a single nucleotide G to A transition and a 10-nucleotide insertion, the latter resulting in a frame-shift mutation in exon 14. |
| Databáze: | OpenAIRE |
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