Conditional loss of Spata7 in photoreceptors causes progressive retinal degeneration in mice.

TitleConditional loss of Spata7 in photoreceptors causes progressive retinal degeneration in mice.
Publication TypeJournal Article
Year of Publication2018
AuthorsEblimit, A, Agrawal, SAkshay, Thomas, K, Anastassov, IAssenov, Abulikemu, T, Moayedi, Y, Mardon, G, Chen, R
JournalExp Eye Res
Date Published2018 Jan
KeywordsAnimals, Cytoskeletal Proteins, Disease Models, Animal, DNA-Binding Proteins, Electroretinography, Mice, Mice, Knockout, Proteins, Retina, Retinal Cone Photoreceptor Cells, Retinal Degeneration, Retinal Rod Photoreceptor Cells, Retinitis Pigmentosa, Rhodopsin

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 Spata7; 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.

Alternate JournalExp Eye Res
PubMed ID29100828
PubMed Central IDPMC5756513
Grant ListR01 EY020540 / EY / NEI NIH HHS / United States
P30 HD024064 / HD / NICHD NIH HHS / United States
P30 EY002520 / EY / NEI NIH HHS / United States
F32 EY024815 / EY / NEI NIH HHS / United States
T32 EY007102 / EY / NEI NIH HHS / United States

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