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Conditional loss of Spata7 in photoreceptors causes progressive retinal degeneration in mice
- Source :
- Experimental Eye Research. 166:120-130
- Publication Year :
- 2018
- Publisher :
- Elsevier BV, 2018.
-
Abstract
- The mammalian retina consists of multiple cell layers including photoreceptor cells, which are light sensing neurons that play essential functions in the visual process. Previously, we identified mutations in SPATA7, encoding spermatogenesis associated protein 7, in families with Leber Congenital Amaurosis (LCA) and juvenile Retinitis Pigmentosa (RP), and showed that Spata7 null mice recapitulate the human disease phenotype of retinal degeneration. SPATA7 is expressed in the connecting cilium of photoreceptor (PR) cells in the mouse retina, as well as in retinal pigment epithelium (RPE) cells, but the functional role of Spata7 in the RPE remains unknown. To investigate whether Spata7 is required in PRs, the RPE, or both, we conditionally knocked out Spata7 in photoreceptors and RPE cells using Crx-Cre and Best1-Cre transgenic mouse lines, respectively. In Spata7 photoreceptor-specific conditional (cKO) mice, both rod and cone photoreceptor dysfunction and degeneration is observed, characterized by progressive thinning of the outer nuclear layer and reduced response to light; however, RPE-specific deletion of Spata7 does not impair retinal function or cell survival. Furthermore, our findings show that both Rhodopsin and RPGRIP1 are mislocalized in the Spata7Flox/-; Crx-Cre cKO mice, suggesting that loss of Spata7 in photoreceptors alone can result in altered trafficking of these proteins in the connecting cilium. Together, our findings suggest that loss of Spata7 in photoreceptors alone is sufficient to cause photoreceptor degeneration, but its function in the RPE is not required for photoreceptor survival; therefore, loss of Spata7 in photoreceptors alters both rod and cone function and survival, consistent with the clinical phenotypes observed in LCA and RP patients with mutations in SPATA7.
- Subjects :
- 0301 basic medicine
Genetically modified mouse
Retinal degeneration
Rhodopsin
genetic structures
Retina
Mice
03 medical and health sciences
Cellular and Molecular Neuroscience
0302 clinical medicine
Retinal Rod Photoreceptor Cells
Retinitis pigmentosa
Electroretinography
medicine
Animals
Outer nuclear layer
Retinal regeneration
Mice, Knockout
Genetics
Gene therapy of the human retina
Retinal pigment epithelium
biology
Retinal Degeneration
Proteins
medicine.disease
eye diseases
Sensory Systems
Cell biology
DNA-Binding Proteins
Cytoskeletal Proteins
Disease Models, Animal
Ophthalmology
030104 developmental biology
medicine.anatomical_structure
Retinal Cone Photoreceptor Cells
030221 ophthalmology & optometry
biology.protein
sense organs
Retinitis Pigmentosa
Subjects
Details
- ISSN :
- 00144835
- Volume :
- 166
- Database :
- OpenAIRE
- Journal :
- Experimental Eye Research
- Accession number :
- edsair.doi.dedup.....a6e9e1ec955b5c6210a3df8763ff5190