Animals deficient in C2Orf71, an autosomal recessive retinitis pigmentosa-associated locus, develop severe early-onset retinal degeneration.

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Genetic mapping of affected individuals resulted in the identification of an uncharacterized gene, C2Orf71, as the causative locus. However, initial homology searches failed to reveal similarities to any previously characterized protein or domain. To address this issue, we characterized the mouse homolog, BC027072. Immunohistochemistry with a custom polyclonal antibody showed staining localized to the inner segments (IS) of photoreceptor cells, as well as the outer segments (OS) of cone cells. A knockout mouse line (BC(-/-)) was generated and demonstrated that loss of this gene results in a severe, early-onset retinal degeneration. Histology and electron microscopy (EM) revealed disorganized OS as early as 3 weeks with complete loss by 24 weeks of age. EM micrographs displayed packets of cellular material containing OS discs or IS organelles in the OS region and abnormal retinal pigmented epithelium cells. Analyses of retinoids and rhodopsin levels showed <20% in BC(-/-) versus wild-type mice early in development. Electroretinograms demonstrated that affected mice were virtually non-responsive to light by 8 weeks of age. Lastly, RNAseq analysis of ocular gene expression in BC(-/-) mice revealed clues to the causes of the progressive retinal degenerations. Although its function remains unknown, this protein appears essential for normal OS development/maintenance and vision in humans and mice. RNAseq data are available in the GEO database under accession: GSE63810.", "claims": [{"id": "claim-target-result", "statement": "RNAseq analysis of ocular gene expression was used, with the source data deposited in the GEO database under accession GSE63810; the headline finding is that the protein appears essential for normal outer-segment development, maintenance, and vision in humans and mice.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:25616964", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Lastly, RNAseq analysis of ocular gene expression in BC−/− mice revealed clues to the causes of the progressive retinal degenerations."}, {"asset": "source:pmid:25616964", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "RNAseq data are available in the GEO database under accession: GSE63810."}, {"asset": "source:pmid:25616964", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Although its function remains unknown, this protein appears essential for normal OS development/maintenance and vision in humans and mice."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "RNAseq analysis of ocular gene expression was used, with the source data deposited in the GEO database under accession GSE63810; the headline finding is that the protein appears essential for normal outer-segment development, maintenance, and vision in humans and mice.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:25616964"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. 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