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Journal Articles Scientific Reports Year : 2022

Analysis of genome-wide knockout mouse database identifies candidate ciliopathy genes

Kendall Higgins
  • Function : Author
Bret A. Moore
  • Function : Author
Zorana Berberovic
  • Function : Author
Hibret A. Adissu
  • Function : Author
Mohammad Eskandarian
  • Function : Author
Ann M. Flenniken
  • Function : Author
Andy Shao
  • Function : Author
Denise M. Imai
  • Function : Author
Dave Clary
  • Function : Author
Louise Lanoue
  • Function : Author
Susan Newbigging
  • Function : Author
Lauryl M. J. Nutter
  • Function : Author
David J. Adams
  • Function : Author
Fatima Bosch
  • Function : Author
Robert E. Braun
  • Function : Author
Steve D. M. Brown
  • Function : Author
Mary E. Dickinson
  • Function : Author
Michael Dobbie
  • Function : Author
Paul Flicek
  • Function : Author
Xiang Gao
  • Function : Author
Sanjeev Galande
  • Function : Author
Anne Grobler
  • Function : Author
Jason D. Heaney
  • Function : Author
Martin Hrabe de Angelis
Hsian-Jean Genie Chin
  • Function : Author
Fabio Mammano
  • Function : Author
Chuan Qin
  • Function : Author
Toshihiko Shiroishi
  • Function : Author
Radislav Sedlacek
  • Function : Author
J.-K. Seong
  • Function : Author
Ying Xu
  • Function : Author
K. C. Kent Lloyd
  • Function : Author
Colin Mckerlie
  • Function : Author
Ala Moshiri
  • Function : Author

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.

Domains

Genetics
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Dates and versions

hal-04217630 , version 1 (25-09-2023)

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Kendall Higgins, Bret A. Moore, Zorana Berberovic, Hibret A. Adissu, Mohammad Eskandarian, et al.. Analysis of genome-wide knockout mouse database identifies candidate ciliopathy genes. Scientific Reports, 2022, 12 (1), ⟨10.1038/s41598-022-19710-7⟩. ⟨hal-04217630⟩
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