Scientific Reports (Dec 2022)
Analysis of genome-wide knockout mouse database identifies candidate ciliopathy genes
- Kendall Higgins,
- Bret A. Moore,
- Zorana Berberovic,
- Hibret A. Adissu,
- Mohammad Eskandarian,
- Ann M. Flenniken,
- Andy Shao,
- Denise M. Imai,
- Dave Clary,
- Louise Lanoue,
- Susan Newbigging,
- Lauryl M. J. Nutter,
- David J. Adams,
- Fatima Bosch,
- Robert E. Braun,
- Steve D. M. Brown,
- Mary E. Dickinson,
- Michael Dobbie,
- Paul Flicek,
- Xiang Gao,
- Sanjeev Galande,
- Anne Grobler,
- Jason D. Heaney,
- Yann Herault,
- Martin Hrabe de Angelis,
- Hsian-Jean Genie Chin,
- Fabio Mammano,
- Chuan Qin,
- Toshihiko Shiroishi,
- Radislav Sedlacek,
- J.-K. Seong,
- Ying Xu,
- The IMPC Consortium,
- K. C. Kent Lloyd,
- Colin McKerlie,
- Ala Moshiri
Affiliations
- Kendall Higgins
- The University of Miami Leonard M. Miller School of Medicine
- Bret A. Moore
- Department of Small Animal Clinical Sciences, University of Florida, College of Veterinary Medicine
- Zorana Berberovic
- The Centre for Phenogenomics
- Hibret A. Adissu
- Covance Inc
- Mohammad Eskandarian
- The Centre for Phenogenomics
- Ann M. Flenniken
- The Centre for Phenogenomics
- Andy Shao
- University of Reno, Nevada, School of Medicine
- Denise M. Imai
- Comparative Pathology Laboratory, U.C. Davis
- Dave Clary
- Mouse Biology Program, U.C. Davis
- Louise Lanoue
- Mouse Biology Program, U.C. Davis
- Susan Newbigging
- The Centre for Phenogenomics
- Lauryl M. J. Nutter
- The Centre for Phenogenomics
- David J. Adams
- The Wellcome Trust Sanger Institute
- Fatima Bosch
- Centre of Animal Biotechnology and Gene Therapy (CBATEG), Universitat Autònoma de Barcelona
- Robert E. Braun
- The Jackson Laboratory
- Steve D. M. Brown
- Medical Research Council Harwell Institute (Mammalian Genetics Unit and Mary Lyon Centre)
- Mary E. Dickinson
- Department of Molecular and Human Genetics, Baylor College of Medicine
- Michael Dobbie
- Phenomics Australia, The Australian National University
- Paul Flicek
- European Molecular Biology Laboratory, European Bioinformatics Institute
- Xiang Gao
- SKL of Pharmaceutical Biotechnology and Model Animal Research Center, Collaborative Innovation Center for Genetics and Development, Nanjing Biomedical Research Institute, Nanjing University
- Sanjeev Galande
- Indian Institutes of Science Education and Research
- Anne Grobler
- Faculty of Health Sciences, PCDDP North-West University
- Jason D. Heaney
- Department of Molecular and Human Genetics, Baylor College of Medicine
- Yann Herault
- Institut de Génétique et de Biologie Moléculaire et Cellulaire, Université de Strasbourg
- Martin Hrabe de Angelis
- German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health
- Hsian-Jean Genie Chin
- National Laboratory Animal Center, National Applied Research Laboratories (NARLabs)
- Fabio Mammano
- Monterotondo Mouse Clinic, Italian National Research Council (CNR), Institute of Cell Biology and Neurobiology
- Chuan Qin
- National Laboratory Animal Center, National Applied Research Laboratories (NARLabs)
- Toshihiko Shiroishi
- RIKEN BioResource Center
- Radislav Sedlacek
- Czech Center for Phenogenomics, Institute of Molecular Genetics of the Czech Academy of Sciences
- J.-K. Seong
- Korea Mouse Phenotyping Consortium (KMPC) and BK21 Program for Veterinary Science, Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University
- Ying Xu
- CAM-SU Genomic Resource Center, Soochow University
- The IMPC Consortium
- K. C. Kent Lloyd
- Mouse Biology Program, U.C. Davis
- Colin McKerlie
- The Hospital for Sick Children
- Ala Moshiri
- Department of Ophthalmology and Vision Science, School of Medicine, U.C. Davis Eye Center
- DOI
- https://doi.org/10.1038/s41598-022-19710-7
- Journal volume & issue
-
Vol. 12,
no. 1
pp. 1 – 17
Abstract
Abstract 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.
