Analysis of genome-wide knockout mouse database identifies candidate ciliopathy genes
Higgins, Kendall (The University of Miami Leonard M. Miller School of Medicine)
Moore, Bret A. (University of Florida. Department of Small Animal Clinical Sciences)
Berberovic, Zorana (Mount Sinai Hospital. Lunenfeld-Tanenbaum Research Institute)
Adissu, Hibret A. (Covance Inc)
Eskandarian, Mohammad (Mount Sinai Hospital. Lunenfeld-Tanenbaum Research Institute)
Flenniken, Ann M. (Mount Sinai Hospital. Lunenfeld-Tanenbaum Research Institute)
Shao, Andy (University of Reno. School of Medicine)
Imai, Denise M. (U.C. Davis. Comparative Pathology Laboratory)
Clary, Dave (U.C. Davis. Mouse Biology Program)
Lanoue, Louise (U.C. Davis. Mouse Biology Program)
Newbigging, Susan (Mount Sinai Hospital. Lunenfeld-Tanenbaum Research Institute)
Nutter, Lauryl M. J. (The Hospital for Sick Children)
Adams, David J. (Wellcome Trust Sanger Institute (Regne Unit))
Bosch i Tubert, Fàtima (Universitat Autònoma de Barcelona. Centre de Biotecnologia Animal i de Teràpia Gènica (CBATEG))
Braun, Robert E. (The Jackson Laboratory)
Brown, Steve D. M. (Medical Research Council Harwell Institute)
Dickinson, Mary E. (Baylor College of Medicine. Department of Molecular and Human Genetics)
Dobbie, Michael (The Australian National University. Phenomics Australia)
Flicek, Paul (European Bioinformatics Institute. European Molecular Biology Laboratory)
Gao, Xiang (Nanjing University. SKL of Pharmaceutical Biotechnology and Model Animal Research Center)
Galande, Sanjeev (Indian Institutes of Science Education and Research)
Grobler, Anne (PCDDP North-West University. Faculty of Health Sciences)
Heaney, Jason D. (Baylor College of Medicine. Department of Molecular and Human Genetics)
Herault, Yann (Université of Strasbourg. Institut Clinique de la Souris)
De Angelis, Martin Hrabe (German Research Center for Environmental Health. German Mouse Clinic)
Chin, Hsian-Jean Genie (National Laboratory Animal Center. National Applied Research Laboratories)
Mammano, Fabio (Institute of Cell Biology and Neurobiology. Monterotondo Mouse Clinic)
Qin, Chuan (Chinese Academy of Medical Science. Institute of Laboratory Animal Sciences)
Shiroishi, Toshihiko (RIKEN BioResource Center)
Sedlacek, Radislav (Institute of Molecular Genetics of the Czech Academy of Sciences. Czech Center for Phenogenomics)
Seong, J.-K. (Seoul National University. Korea Mouse Phenotyping Consortium)
Xu, Ying (Soochow University. CAM-SU Genomic Resource Center)
Lloyd, K. C. Kent (U.C. Davis. Department of Surgery, School of Medicine)
McKerlie, Colin (Hospital for Sick Children)
Moshiri, Ala (U.C. Davis Eye Center. Department of Ophthalmology and Vision Science, School of Medicine)

Data:	2022
Resum:	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.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Cell biology ; Organelles ; Molecular medicine ; Ciliogenesis
Publicat a:	Scientific reports, Vol. 12 (december 2022) , ISSN 2045-2322

DOI: 10.1038/s41598-022-19710-7
PMID: 36456625

17 p, 6.0 MB

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