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Exp Eye Res. 2018 Jan;166:120-130. doi: 10.1016/j.exer.2017.10.015. Epub 2017 Oct 31.

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

Author information

1
Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030-3411, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030-3411, USA.
2
Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030-3411, USA.
3
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030-3411, USA; The Key Laboratory of Plant Resources and Chemistry of Arid Zone, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi, Xinjiang, 830011, China.
4
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030-3411, USA; Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030-3411, USA; Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030-3411, USA. Electronic address: gmardon@bcm.edu.
5
Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030-3411, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030-3411, USA. Electronic address: ruichen@bcm.edu.

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.

KEYWORDS:

Conditional knockout; Leber Congenital Amaurosis; Photoreceptors; RPE; Retinal degeneration; Retinal function; Retinitis Pigmentosa; SPATA7

PMID:
29100828
PMCID:
PMC5756513
DOI:
10.1016/j.exer.2017.10.015
[Indexed for MEDLINE]
Free PMC Article

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