Advertisement
Combining Cep290 and Mkks ciliopathy alleles in mice rescues sensory defects and restores ciliogenesis
Rivka A. Rachel,1 Helen L. May-Simera,2 Shobi Veleri,1 Norimoto Gotoh,1 Byung Yoon Choi,3 Carlos Murga-Zamalloa,4 Jeremy C. McIntyre,5 Jonah Marek,6 Irma Lopez,6 Alice N. Hackett,1 Jun Zhang,7 Matthew Brooks,1 Anneke I. den Hollander,8 Philip L. Beales,9 Tiansen Li,1 Samuel G. Jacobson,10 Raman Sood,11 Jeffrey R. Martens,5 Paul Liu,11 Thomas B. Friedman,3 Hemant Khanna,4 Robert K. Koenekoop,6 Matthew W. Kelley,2 and Anand Swaroop1
1Neurobiology Neurodegeneration and Repair Laboratory, National Eye Institute, NIH, Bethesda, Maryland, USA. 2Laboratory of Cochlear Development and 3Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, Maryland, USA. 4Department of Ophthalmology and Visual Sciences and 5Department of Pharmacology, University of Michigan, Ann Arbor, Michigan, USA. 6McGill Ocular Genetics Laboratory and Pediatric Ophthalmology, McGill University Health Centre, Montreal, Quebec, Canada. 7National Eye Institute Histopathology Core Facility, NIH, Bethesda, Maryland, USA. 8Departments of Ophthalmology and Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. 9Molecular Medicine Unit, UCL Institute of Child Health, London, United Kingdom. 10Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania, USA. 11Genetics and Molecular Biology Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA.
Find articles by Rachel, R. in: JCI | PubMed | Google Scholar
1Neurobiology Neurodegeneration and Repair Laboratory, National Eye Institute, NIH, Bethesda, Maryland, USA. 2Laboratory of Cochlear Development and 3Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, Maryland, USA. 4Department of Ophthalmology and Visual Sciences and 5Department of Pharmacology, University of Michigan, Ann Arbor, Michigan, USA. 6McGill Ocular Genetics Laboratory and Pediatric Ophthalmology, McGill University Health Centre, Montreal, Quebec, Canada. 7National Eye Institute Histopathology Core Facility, NIH, Bethesda, Maryland, USA. 8Departments of Ophthalmology and Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. 9Molecular Medicine Unit, UCL Institute of Child Health, London, United Kingdom. 10Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania, USA. 11Genetics and Molecular Biology Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA.
Find articles by May-Simera, H. in: JCI | PubMed | Google Scholar
1Neurobiology Neurodegeneration and Repair Laboratory, National Eye Institute, NIH, Bethesda, Maryland, USA. 2Laboratory of Cochlear Development and 3Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, Maryland, USA. 4Department of Ophthalmology and Visual Sciences and 5Department of Pharmacology, University of Michigan, Ann Arbor, Michigan, USA. 6McGill Ocular Genetics Laboratory and Pediatric Ophthalmology, McGill University Health Centre, Montreal, Quebec, Canada. 7National Eye Institute Histopathology Core Facility, NIH, Bethesda, Maryland, USA. 8Departments of Ophthalmology and Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. 9Molecular Medicine Unit, UCL Institute of Child Health, London, United Kingdom. 10Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania, USA. 11Genetics and Molecular Biology Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA.
Find articles by Veleri, S. in: JCI | PubMed | Google Scholar
1Neurobiology Neurodegeneration and Repair Laboratory, National Eye Institute, NIH, Bethesda, Maryland, USA. 2Laboratory of Cochlear Development and 3Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, Maryland, USA. 4Department of Ophthalmology and Visual Sciences and 5Department of Pharmacology, University of Michigan, Ann Arbor, Michigan, USA. 6McGill Ocular Genetics Laboratory and Pediatric Ophthalmology, McGill University Health Centre, Montreal, Quebec, Canada. 7National Eye Institute Histopathology Core Facility, NIH, Bethesda, Maryland, USA. 8Departments of Ophthalmology and Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. 9Molecular Medicine Unit, UCL Institute of Child Health, London, United Kingdom. 10Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania, USA. 11Genetics and Molecular Biology Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA.
Find articles by Gotoh, N. in: JCI | PubMed | Google Scholar
1Neurobiology Neurodegeneration and Repair Laboratory, National Eye Institute, NIH, Bethesda, Maryland, USA. 2Laboratory of Cochlear Development and 3Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, Maryland, USA. 4Department of Ophthalmology and Visual Sciences and 5Department of Pharmacology, University of Michigan, Ann Arbor, Michigan, USA. 6McGill Ocular Genetics Laboratory and Pediatric Ophthalmology, McGill University Health Centre, Montreal, Quebec, Canada. 7National Eye Institute Histopathology Core Facility, NIH, Bethesda, Maryland, USA. 8Departments of Ophthalmology and Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. 9Molecular Medicine Unit, UCL Institute of Child Health, London, United Kingdom. 10Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania, USA. 11Genetics and Molecular Biology Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA.
Find articles by Choi, B. in: JCI | PubMed | Google Scholar
1Neurobiology Neurodegeneration and Repair Laboratory, National Eye Institute, NIH, Bethesda, Maryland, USA. 2Laboratory of Cochlear Development and 3Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, Maryland, USA. 4Department of Ophthalmology and Visual Sciences and 5Department of Pharmacology, University of Michigan, Ann Arbor, Michigan, USA. 6McGill Ocular Genetics Laboratory and Pediatric Ophthalmology, McGill University Health Centre, Montreal, Quebec, Canada. 7National Eye Institute Histopathology Core Facility, NIH, Bethesda, Maryland, USA. 8Departments of Ophthalmology and Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. 9Molecular Medicine Unit, UCL Institute of Child Health, London, United Kingdom. 10Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania, USA. 11Genetics and Molecular Biology Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA.
Find articles by Murga-Zamalloa, C. in: JCI | PubMed | Google Scholar
1Neurobiology Neurodegeneration and Repair Laboratory, National Eye Institute, NIH, Bethesda, Maryland, USA. 2Laboratory of Cochlear Development and 3Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, Maryland, USA. 4Department of Ophthalmology and Visual Sciences and 5Department of Pharmacology, University of Michigan, Ann Arbor, Michigan, USA. 6McGill Ocular Genetics Laboratory and Pediatric Ophthalmology, McGill University Health Centre, Montreal, Quebec, Canada. 7National Eye Institute Histopathology Core Facility, NIH, Bethesda, Maryland, USA. 8Departments of Ophthalmology and Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. 9Molecular Medicine Unit, UCL Institute of Child Health, London, United Kingdom. 10Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania, USA. 11Genetics and Molecular Biology Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA.
Find articles by McIntyre, J. in: JCI | PubMed | Google Scholar
1Neurobiology Neurodegeneration and Repair Laboratory, National Eye Institute, NIH, Bethesda, Maryland, USA. 2Laboratory of Cochlear Development and 3Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, Maryland, USA. 4Department of Ophthalmology and Visual Sciences and 5Department of Pharmacology, University of Michigan, Ann Arbor, Michigan, USA. 6McGill Ocular Genetics Laboratory and Pediatric Ophthalmology, McGill University Health Centre, Montreal, Quebec, Canada. 7National Eye Institute Histopathology Core Facility, NIH, Bethesda, Maryland, USA. 8Departments of Ophthalmology and Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. 9Molecular Medicine Unit, UCL Institute of Child Health, London, United Kingdom. 10Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania, USA. 11Genetics and Molecular Biology Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA.
Find articles by Marek, J. in: JCI | PubMed | Google Scholar
1Neurobiology Neurodegeneration and Repair Laboratory, National Eye Institute, NIH, Bethesda, Maryland, USA. 2Laboratory of Cochlear Development and 3Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, Maryland, USA. 4Department of Ophthalmology and Visual Sciences and 5Department of Pharmacology, University of Michigan, Ann Arbor, Michigan, USA. 6McGill Ocular Genetics Laboratory and Pediatric Ophthalmology, McGill University Health Centre, Montreal, Quebec, Canada. 7National Eye Institute Histopathology Core Facility, NIH, Bethesda, Maryland, USA. 8Departments of Ophthalmology and Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. 9Molecular Medicine Unit, UCL Institute of Child Health, London, United Kingdom. 10Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania, USA. 11Genetics and Molecular Biology Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA.
Find articles by Lopez, I. in: JCI | PubMed | Google Scholar
1Neurobiology Neurodegeneration and Repair Laboratory, National Eye Institute, NIH, Bethesda, Maryland, USA. 2Laboratory of Cochlear Development and 3Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, Maryland, USA. 4Department of Ophthalmology and Visual Sciences and 5Department of Pharmacology, University of Michigan, Ann Arbor, Michigan, USA. 6McGill Ocular Genetics Laboratory and Pediatric Ophthalmology, McGill University Health Centre, Montreal, Quebec, Canada. 7National Eye Institute Histopathology Core Facility, NIH, Bethesda, Maryland, USA. 8Departments of Ophthalmology and Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. 9Molecular Medicine Unit, UCL Institute of Child Health, London, United Kingdom. 10Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania, USA. 11Genetics and Molecular Biology Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA.
Find articles by Hackett, A. in: JCI | PubMed | Google Scholar
1Neurobiology Neurodegeneration and Repair Laboratory, National Eye Institute, NIH, Bethesda, Maryland, USA. 2Laboratory of Cochlear Development and 3Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, Maryland, USA. 4Department of Ophthalmology and Visual Sciences and 5Department of Pharmacology, University of Michigan, Ann Arbor, Michigan, USA. 6McGill Ocular Genetics Laboratory and Pediatric Ophthalmology, McGill University Health Centre, Montreal, Quebec, Canada. 7National Eye Institute Histopathology Core Facility, NIH, Bethesda, Maryland, USA. 8Departments of Ophthalmology and Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. 9Molecular Medicine Unit, UCL Institute of Child Health, London, United Kingdom. 10Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania, USA. 11Genetics and Molecular Biology Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA.
Find articles by Zhang, J. in: JCI | PubMed | Google Scholar
1Neurobiology Neurodegeneration and Repair Laboratory, National Eye Institute, NIH, Bethesda, Maryland, USA. 2Laboratory of Cochlear Development and 3Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, Maryland, USA. 4Department of Ophthalmology and Visual Sciences and 5Department of Pharmacology, University of Michigan, Ann Arbor, Michigan, USA. 6McGill Ocular Genetics Laboratory and Pediatric Ophthalmology, McGill University Health Centre, Montreal, Quebec, Canada. 7National Eye Institute Histopathology Core Facility, NIH, Bethesda, Maryland, USA. 8Departments of Ophthalmology and Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. 9Molecular Medicine Unit, UCL Institute of Child Health, London, United Kingdom. 10Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania, USA. 11Genetics and Molecular Biology Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA.
Find articles by Brooks, M. in: JCI | PubMed | Google Scholar
1Neurobiology Neurodegeneration and Repair Laboratory, National Eye Institute, NIH, Bethesda, Maryland, USA. 2Laboratory of Cochlear Development and 3Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, Maryland, USA. 4Department of Ophthalmology and Visual Sciences and 5Department of Pharmacology, University of Michigan, Ann Arbor, Michigan, USA. 6McGill Ocular Genetics Laboratory and Pediatric Ophthalmology, McGill University Health Centre, Montreal, Quebec, Canada. 7National Eye Institute Histopathology Core Facility, NIH, Bethesda, Maryland, USA. 8Departments of Ophthalmology and Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. 9Molecular Medicine Unit, UCL Institute of Child Health, London, United Kingdom. 10Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania, USA. 11Genetics and Molecular Biology Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA.
Find articles by den Hollander, A. in: JCI | PubMed | Google Scholar
1Neurobiology Neurodegeneration and Repair Laboratory, National Eye Institute, NIH, Bethesda, Maryland, USA. 2Laboratory of Cochlear Development and 3Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, Maryland, USA. 4Department of Ophthalmology and Visual Sciences and 5Department of Pharmacology, University of Michigan, Ann Arbor, Michigan, USA. 6McGill Ocular Genetics Laboratory and Pediatric Ophthalmology, McGill University Health Centre, Montreal, Quebec, Canada. 7National Eye Institute Histopathology Core Facility, NIH, Bethesda, Maryland, USA. 8Departments of Ophthalmology and Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. 9Molecular Medicine Unit, UCL Institute of Child Health, London, United Kingdom. 10Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania, USA. 11Genetics and Molecular Biology Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA.
Find articles by Beales, P. in: JCI | PubMed | Google Scholar
1Neurobiology Neurodegeneration and Repair Laboratory, National Eye Institute, NIH, Bethesda, Maryland, USA. 2Laboratory of Cochlear Development and 3Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, Maryland, USA. 4Department of Ophthalmology and Visual Sciences and 5Department of Pharmacology, University of Michigan, Ann Arbor, Michigan, USA. 6McGill Ocular Genetics Laboratory and Pediatric Ophthalmology, McGill University Health Centre, Montreal, Quebec, Canada. 7National Eye Institute Histopathology Core Facility, NIH, Bethesda, Maryland, USA. 8Departments of Ophthalmology and Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. 9Molecular Medicine Unit, UCL Institute of Child Health, London, United Kingdom. 10Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania, USA. 11Genetics and Molecular Biology Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA.
Find articles by Li, T. in: JCI | PubMed | Google Scholar
1Neurobiology Neurodegeneration and Repair Laboratory, National Eye Institute, NIH, Bethesda, Maryland, USA. 2Laboratory of Cochlear Development and 3Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, Maryland, USA. 4Department of Ophthalmology and Visual Sciences and 5Department of Pharmacology, University of Michigan, Ann Arbor, Michigan, USA. 6McGill Ocular Genetics Laboratory and Pediatric Ophthalmology, McGill University Health Centre, Montreal, Quebec, Canada. 7National Eye Institute Histopathology Core Facility, NIH, Bethesda, Maryland, USA. 8Departments of Ophthalmology and Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. 9Molecular Medicine Unit, UCL Institute of Child Health, London, United Kingdom. 10Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania, USA. 11Genetics and Molecular Biology Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA.
Find articles by Jacobson, S. in: JCI | PubMed | Google Scholar
1Neurobiology Neurodegeneration and Repair Laboratory, National Eye Institute, NIH, Bethesda, Maryland, USA. 2Laboratory of Cochlear Development and 3Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, Maryland, USA. 4Department of Ophthalmology and Visual Sciences and 5Department of Pharmacology, University of Michigan, Ann Arbor, Michigan, USA. 6McGill Ocular Genetics Laboratory and Pediatric Ophthalmology, McGill University Health Centre, Montreal, Quebec, Canada. 7National Eye Institute Histopathology Core Facility, NIH, Bethesda, Maryland, USA. 8Departments of Ophthalmology and Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. 9Molecular Medicine Unit, UCL Institute of Child Health, London, United Kingdom. 10Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania, USA. 11Genetics and Molecular Biology Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA.
Find articles by Sood, R. in: JCI | PubMed | Google Scholar
1Neurobiology Neurodegeneration and Repair Laboratory, National Eye Institute, NIH, Bethesda, Maryland, USA. 2Laboratory of Cochlear Development and 3Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, Maryland, USA. 4Department of Ophthalmology and Visual Sciences and 5Department of Pharmacology, University of Michigan, Ann Arbor, Michigan, USA. 6McGill Ocular Genetics Laboratory and Pediatric Ophthalmology, McGill University Health Centre, Montreal, Quebec, Canada. 7National Eye Institute Histopathology Core Facility, NIH, Bethesda, Maryland, USA. 8Departments of Ophthalmology and Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. 9Molecular Medicine Unit, UCL Institute of Child Health, London, United Kingdom. 10Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania, USA. 11Genetics and Molecular Biology Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA.
Find articles by Martens, J. in: JCI | PubMed | Google Scholar
1Neurobiology Neurodegeneration and Repair Laboratory, National Eye Institute, NIH, Bethesda, Maryland, USA. 2Laboratory of Cochlear Development and 3Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, Maryland, USA. 4Department of Ophthalmology and Visual Sciences and 5Department of Pharmacology, University of Michigan, Ann Arbor, Michigan, USA. 6McGill Ocular Genetics Laboratory and Pediatric Ophthalmology, McGill University Health Centre, Montreal, Quebec, Canada. 7National Eye Institute Histopathology Core Facility, NIH, Bethesda, Maryland, USA. 8Departments of Ophthalmology and Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. 9Molecular Medicine Unit, UCL Institute of Child Health, London, United Kingdom. 10Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania, USA. 11Genetics and Molecular Biology Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA.
Find articles by Liu, P. in: JCI | PubMed | Google Scholar
1Neurobiology Neurodegeneration and Repair Laboratory, National Eye Institute, NIH, Bethesda, Maryland, USA. 2Laboratory of Cochlear Development and 3Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, Maryland, USA. 4Department of Ophthalmology and Visual Sciences and 5Department of Pharmacology, University of Michigan, Ann Arbor, Michigan, USA. 6McGill Ocular Genetics Laboratory and Pediatric Ophthalmology, McGill University Health Centre, Montreal, Quebec, Canada. 7National Eye Institute Histopathology Core Facility, NIH, Bethesda, Maryland, USA. 8Departments of Ophthalmology and Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. 9Molecular Medicine Unit, UCL Institute of Child Health, London, United Kingdom. 10Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania, USA. 11Genetics and Molecular Biology Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA.
Find articles by Friedman, T. in: JCI | PubMed | Google Scholar
1Neurobiology Neurodegeneration and Repair Laboratory, National Eye Institute, NIH, Bethesda, Maryland, USA. 2Laboratory of Cochlear Development and 3Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, Maryland, USA. 4Department of Ophthalmology and Visual Sciences and 5Department of Pharmacology, University of Michigan, Ann Arbor, Michigan, USA. 6McGill Ocular Genetics Laboratory and Pediatric Ophthalmology, McGill University Health Centre, Montreal, Quebec, Canada. 7National Eye Institute Histopathology Core Facility, NIH, Bethesda, Maryland, USA. 8Departments of Ophthalmology and Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. 9Molecular Medicine Unit, UCL Institute of Child Health, London, United Kingdom. 10Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania, USA. 11Genetics and Molecular Biology Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA.
Find articles by Khanna, H. in: JCI | PubMed | Google Scholar
1Neurobiology Neurodegeneration and Repair Laboratory, National Eye Institute, NIH, Bethesda, Maryland, USA. 2Laboratory of Cochlear Development and 3Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, Maryland, USA. 4Department of Ophthalmology and Visual Sciences and 5Department of Pharmacology, University of Michigan, Ann Arbor, Michigan, USA. 6McGill Ocular Genetics Laboratory and Pediatric Ophthalmology, McGill University Health Centre, Montreal, Quebec, Canada. 7National Eye Institute Histopathology Core Facility, NIH, Bethesda, Maryland, USA. 8Departments of Ophthalmology and Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. 9Molecular Medicine Unit, UCL Institute of Child Health, London, United Kingdom. 10Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania, USA. 11Genetics and Molecular Biology Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA.
Find articles by Koenekoop, R. in: JCI | PubMed | Google Scholar
1Neurobiology Neurodegeneration and Repair Laboratory, National Eye Institute, NIH, Bethesda, Maryland, USA. 2Laboratory of Cochlear Development and 3Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, Maryland, USA. 4Department of Ophthalmology and Visual Sciences and 5Department of Pharmacology, University of Michigan, Ann Arbor, Michigan, USA. 6McGill Ocular Genetics Laboratory and Pediatric Ophthalmology, McGill University Health Centre, Montreal, Quebec, Canada. 7National Eye Institute Histopathology Core Facility, NIH, Bethesda, Maryland, USA. 8Departments of Ophthalmology and Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. 9Molecular Medicine Unit, UCL Institute of Child Health, London, United Kingdom. 10Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania, USA. 11Genetics and Molecular Biology Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA.
Find articles by Kelley, M. in: JCI | PubMed | Google Scholar
1Neurobiology Neurodegeneration and Repair Laboratory, National Eye Institute, NIH, Bethesda, Maryland, USA. 2Laboratory of Cochlear Development and 3Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, Maryland, USA. 4Department of Ophthalmology and Visual Sciences and 5Department of Pharmacology, University of Michigan, Ann Arbor, Michigan, USA. 6McGill Ocular Genetics Laboratory and Pediatric Ophthalmology, McGill University Health Centre, Montreal, Quebec, Canada. 7National Eye Institute Histopathology Core Facility, NIH, Bethesda, Maryland, USA. 8Departments of Ophthalmology and Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. 9Molecular Medicine Unit, UCL Institute of Child Health, London, United Kingdom. 10Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania, USA. 11Genetics and Molecular Biology Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA.
Find articles by Swaroop, A. in: JCI | PubMed | Google Scholar
First published August 1, 2012 - More info
J Clin Invest. 2012;122(8):3025–3025. https://doi.org/10.1172/JCI65432.
© 2012 The American Society for Clinical Investigation
Related article:
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.
Authors
Rivka A. Rachel, Helen L. May-Simera, Shobi Veleri, Norimoto Gotoh, Byung Yoon Choi, Carlos Murga-Zamalloa, Jeremy C. McIntyre, Jonah Marek, Irma Lopez, Alice N. Hackett, Matthew Brooks, Anneke I. den Hollander, Philip L. Beales, Tiansen Li, Samuel G. Jacobson, Raman Sood, Jeffrey R. Martens, Paul Liu, Thomas B. Friedman, Hemant Khanna, Robert K. Koenekoop, Matthew W. Kelley, Anand Swaroop
Original citation: J. Clin. Invest. 2012;122(4):1233–1245. doi:10.1172/JCI60981.
Citation for this corrigendum: J. Clin. Invest. 2012;122(8):3025. doi:10.1172/JCI65432.
During the preparation of this manuscript, Jun Zhang’s name was inadvertently omitted from the author list, and his present address was not given. The correct author and affiliations list is above. The correct present address is below.
Jun Zhang’s present address is: National Institute of Neurological Disease and Stroke, NIH, Bethesda, Maryland, USA.
The authors regret the error.
Copyright © 2020 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)