ArticleThe Journal of clinical investigation2012
Combining Cep290 and Mkks ciliopathy alleles in mice rescues sensory defects and restores ciliogenesis.
Article in The Journal of clinical investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 57 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
57 citing papers in PubMed.
- Revisiting retinal and macular degeneration in the genomics era.Nature reviews. Genetics · 2026Review
- Article
- Article
- Cell-cell interaction in the pathogenesis of inherited retinal diseases.Frontiers in cell and developmental biology · 2024Review
- Cellular and Molecular Mechanisms of Pathogenesis Underlying Inherited Retinal Dystrophies.Biomolecules · 2023Review
- Potential therapeutic strategies for photoreceptor degeneration: the path to restore vision.Journal of translational medicine · 2022Review
- Fetal ciliopathies: a retrospective observational single-center study.Archives of gynecology and obstetrics · 2022Observational
- An accurate prediction model of digenic interaction for estimating pathogenic gene pairs of human diseases.Computational and structural biotechnology journal · 2022Article
- Genetic compensation for cilia defects in cep290 mutants by upregulation of cilia-associated small GTPases.Journal of cell science · 2021Article
- Primary cilia biogenesis and associated retinal ciliopathies.Seminars in cell & developmental biology · 2021Review
- Dysregulation of sonic hedgehog signaling causes hearing loss in ciliopathy mouse models.eLife · 2020Article
- The GENDULF algorithm: mining transcriptomics to uncover modifier genes for monogenic diseases.Molecular systems biology · 2020Article
- Review
- Ciliary Genes in Renal Cystic Diseases.Cells · 2020Review
- Limitations and Promise of Retinal Tissue From Human Pluripotent Stem Cells for Developing Therapies of Blindness.Frontiers in cellular neuroscience · 2020Review
- The myosin-tail homology domain of centrosomal protein 290 is essential for protein confinement between the inner and outer segments in photoreceptors.The Journal of biological chemistry · 2019Article
- Retinal disease in ciliopathies: Recent advances with a focus on stem cell-based therapies.Translational science of rare diseases · 2019Article
- Deletion of both centrin 2 (CETN2) and CETN3 destabilizes the distal connecting cilium of mouse photoreceptors.The Journal of biological chemistry · 2019Article
- Ocular Ciliopathies: Genetic and Mechanistic Insights into Developing Therapies.Current medicinal chemistry · 2019Review
- Article
Corrections and comments
- Commented on by
- Erratum issuedZhang, Jun [added]
Authors and funding
24 authors.
Funding
Abstract
Cilia are highly specialized microtubule-based organelles that have pivotal roles in numerous biological processes, including transducing sensory signals. Defects in cilia biogenesis and transport cause pleiotropic human ciliopathies. Mutations in over 30 different genes can lead to cilia defects, and complex interactions exist among ciliopathy-associated proteins. Mutations of the centrosomal protein 290 kDa (CEP290) lead to distinct clinical manifestations, including Leber congenital amaurosis (LCA), a hereditary cause of blindness due to photoreceptor degeneration. Mice homozygous for a mutant Cep290 allele (Cep290rd16 mice) exhibit LCA-like early-onset retinal degeneration that is caused by an in-frame deletion in the CEP290 protein. Here, we show that the domain deleted in the protein encoded by the Cep290rd16 allele directly interacts with another ciliopathy protein, MKKS. MKKS mutations identified in patients with the ciliopathy Bardet-Biedl syndrome disrupted this interaction. In zebrafish embryos, combined subminimal knockdown of mkks and cep290 produced sensory defects in the eye and inner ear. Intriguingly, combinations of Cep290rd16 and Mkksko alleles in mice led to improved ciliogenesis and sensory functions compared with those of either mutant alone. We propose that altered association of CEP290 and MKKS affects the integrity of multiprotein complexes at the cilia transition zone and basal body. Amelioration of the sensory phenotypes caused by specific mutations in one protein by removal of an interacting domain/protein suggests a possible novel approach for treating human ciliopathies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.