Accelerating functional gene discovery in osteoarthritis
Natalie C Butterfield,
Katherine F Curry,
Naila S Mannan,
Victoria D Leitch,
John G Logan,
Julian A Waung,
Scott E Youlten,
J Mark Wilkinson,
Elizabeth A McAninch,
Valerie E Vancollie,
Jacqueline K. White,
Christopher J Lelliott,
David J. Adams,
Antonio C. Bianco,
Peter I Croucher,
Graham R Williams,
J H Duncan Bassett
Posted 10 Nov 2019
bioRxiv DOI: 10.1101/836221
Posted 10 Nov 2019
Osteoarthritis causes debilitating pain and disability, resulting in a huge 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 unselected 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 generate 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. This expanding resource of unselected mutant mice will transform the field by accelerating functional gene discovery in osteoarthritis and offering unanticipated drug discovery opportunities for this common and incapacitating chronic disease.
- Downloaded 585 times
- Download rankings, all-time:
- Site-wide: 35,696 out of 117,931
- In genetics: 1,807 out of 5,127
- Year to date:
- Site-wide: 28,408 out of 117,931
- Since beginning of last month:
- Site-wide: 34,754 out of 117,931
Downloads over time
Distribution of downloads per paper, site-wide
- 27 Nov 2020: The website and API now include results pulled from medRxiv as well as bioRxiv.
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!