We searched a database of single-gene knockout (KO) mice produced by the International Mouse Phenotyping Consortium (IMPC) to identify candidate ciliopathy genes. We first screened for phenotypes in mouse lines with both ocular and renal or reproductive trait abnormalities. The STRING protein interaction tool was used to identify interactions between known cilia gene products and those encoded by the genes in individual knockout mouse strains in order to generate a list of "candidate ciliopathy genes." From this list, 32 genes encoded proteins predicted to interact with known ciliopathy proteins. Of these, 25 had no previously described roles in ciliary pathobiology. Histological and morphological evidence of phenotypes found in ciliopathies in knockout mouse lines are presented as examples (genes Abi2, Wdr62, Ap4e1, Dync1li1, and Prkab1). Phenotyping data and descriptions generated on IMPC mouse line are useful for mechanistic studies, target discovery, rare disease diagnosis, and preclinical therapeutic development trials. Here we demonstrate the effective use of the IMPC phenotype data to uncover genes with no previous role in ciliary biology, which may be clinically relevant for identification of novel disease genes implicated in ciliopathies.

CAM SU Genomic Resource Center Soochow University Organization Planning of No 1 Shizi Street Suzhou 215123 China

CELPHEDIA PHENOMIN Institut Clinique de la Souris CNRS INSERM Université of Strasbourg 1 rue Laurent Fries 67404 Illkirch Graffenstaden France

Centre National de la Recherche Scientifique UMR7104 Illkirch France

Centre of Animal Biotechnology and Gene Therapy Universitat Autònoma de Barcelona 08193 Barcelona Spain

Comparative Pathology Laboratory U C Davis Davis 95616 USA

Covance Inc Chantilly VA 20151 USA

Czech Center for Phenogenomics Institute of Molecular Genetics of the Czech Academy of Sciences IMG BIOCEV Building SO 02 Prumyslova 595 252 50 Vestec Czech Republic

Department of Laboratory Medicine and Pathobiology Hospital for Sick Children The Centre for Phenogenomics Faculty of Medicine University of Toronto 25 Orde Street Toronto ON M5T 3H7 USA

Department of Molecular and Human Genetics Baylor College of Medicine Houston TX 77030 USA

Department of Ophthalmology and Vision Science School of Medicine U C Davis Eye Center 4860 Y Street Suite 2400 Sacramento CA 95817 USA

Department of Small Animal Clinical Sciences University of Florida College of Veterinary Medicine Gainesville FL 32608 USA

Department of Surgery School of Medicine U C Davis Sacramento CA 95817 USA

European Molecular Biology Laboratory European Bioinformatics Institute Wellcome Genome Campus Hinxton Cambridge CB10 1SD UK

Faculty of Health Sciences PCDDP North West University North West University Potchefstroom Campus 11 Hoffman Street Potchefstroom 2531 South Africa

German Mouse Clinic Institute of Experimental Genetics Helmholtz Zentrum München German Research Center for Environmental Health Ingolstädter Landstraße 1 85764 Neuherberg Germany

Indian Institutes of Science Education and Research Dr Homi Bhabha Rd Ward No 8 NCL Colony Pashan Pune Maharashtra 411008 India

Institut de Génétique et de Biologie Moléculaire et Cellulaire Université de Strasbourg 1 rue Laurent Fries 67404 Illkirch France

Institut de Génétique et de Biologie Moléculaire et Cellulaire Université de Strasbourg 67400 Illkirch France

Institut National de la Santé et de la Recherche Médicale U1258 Illkirch France

Institute of Laboratory Animal Sciences Chinese Academy of Medical Science 5 Panjiayuan Nanli Chaoyang District Beijing 100021 China

Korea Mouse Phenotyping Consortium and BK21 Program for Veterinary Science Research Institute for Veterinary Science College of Veterinary Medicine Seoul National University 599 Gwanangno Gwanak gu Seoul 08826 South Korea

Lunenfeld Tanenbaum Research Institute Mount Sinai Hospital Toronto ON M5G 1X5 Canada

Medical Research Council Harwell Institute Harwell Campus Oxfordshire OX11 0RD UK

Monterotondo Mouse Clinic Italian National Research Council Institute of Cell Biology and Neurobiology Adriano Buzzati Traverso Campus Via Ramarini 00015 Monterotondo Scalo Italy

Mouse Biology Program U C Davis Davis CA 95618 USA

National Laboratory Animal Center National Applied Research Laboratories

National Laboratory Animal Center National Applied Research Laboratories Beijing China

Phenomics Australia The Australian National University 131 Garran Rd Acton Canberra ACT 2601 Australia

RIKEN BioResource Center Tsukuba Ibaraki 305 0074 Japan

SKL of Pharmaceutical Biotechnology and Model Animal Research Center Collaborative Innovation Center for Genetics and Development Nanjing Biomedical Research Institute Nanjing University Nanjing 210061 China

The Centre for Phenogenomics Toronto ON Canada

The Hospital for Sick Children 555 University Avenue Toronto ON M5G 1X8 Canada

The Jackson Laboratory Bar Harbor ME 04609 USA

The University of Miami Leonard M Miller School of Medicine Miami FL 33136 USA

The Wellcome Trust Sanger Institute Wellcome Genome Campus Hinxton Cambridge CB10 1SA UK

Université de Strasbourg 1 rue Laurent Fries 67404 Illkirch France

University of Reno Nevada School of Medicine Reno NV 89557 USA

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