Document Type
Article
Publication Date
1-20-2021
Keywords
JMG
JAX Source
Nat Commun 2021 Jan 20; 12(1):467
Volume
12
Issue
1
First Page
467
Last Page
467
ISSN
2041-1723
PMID
33473114
DOI
https://doi.org/10.1038/s41467-020-20761-5
Abstract
Osteoarthritis causes debilitating pain and disability, resulting in a considerable socioeconomic burden, yet no drugs are available that prevent disease onset or progression. Here, we develop, validate and use rapid-throughput imaging techniques to identify abnormal joint phenotypes in randomly selected mutant mice generated by the International Knockout Mouse Consortium. We identify 14 genes with functional involvement in osteoarthritis pathogenesis, including the homeobox gene Pitx1, and functionally characterize 6 candidate human osteoarthritis genes in mouse models. We demonstrate sensitivity of the methods by identifying age-related degenerative joint damage in wild-type mice. Finally, we phenotype previously generated mutant mice with an osteoarthritis-associated polymorphism in the Dio2 gene by CRISPR/Cas9 genome editing and demonstrate a protective role in disease onset with public health implications. We hope this expanding resource of mutant mice will accelerate functional gene discovery in osteoarthritis and offer drug discovery opportunities for this common, incapacitating chronic disease.
Recommended Citation
Butterfield N,
Curry K,
Steinberg J,
Dewhurst H,
Komla-Ebri D,
Mannan N,
Adoum A,
Leitch V,
Logan J,
Waung J,
Ghirardello E,
Southam L,
Youlten S,
Wilkinson J,
McAninch E,
Vancollie V,
Kussy F,
White J,
Lelliott C,
Adams D,
Jacques R,
Bianco A,
Boyde A,
Zeggini E,
Croucher P,
Williams G,
Bassett J.
Accelerating functional gene discovery in osteoarthritis. Nat Commun 2021 Jan 20; 12(1):467
Comments
This article is licensed under a Creative Commons Attribution 4.0 International License.