• Pain · Jun 2022

    Identifying genetic determinants of inflammatory pain in mice using a large-scale gene-targeted screen.

    • Janine M Wotton, Emma Peterson, Ann M Flenniken, Rasneer S Bains, Surabi Veeraragavan, Lynette R Bower, Jason A Bubier, Marc Parisien, Alexandr Bezginov, Hamed Haselimashhadi, Jeremy Mason, Michayla A Moore, Michelle E Stewart, Dave A Clary, Daniel J Delbarre, Laura C Anderson, Abigail D'Souza, Leslie O Goodwin, Mark E Harrison, Ziyue Huang, Matthew Mckay, Dawei Qu, Luis Santos, Subhiksha Srinivasan, Rachel Urban, Igor Vukobradovic, Christopher S Ward, Amelia M Willett, Robert E Braun, BrownSteve D MSDM0000-0002-0617-4824Mammalian Genetics Unit, MRC Harwell Institute, Didcot, Oxfordshire, United Kingdom., Mary E Dickinson, Jason D Heaney, Vivek Kumar, LloydK C KentKCK0000-0002-5318-4144Mouse Biology Program, University of California-Davis, Davis, CA, United States.Department of Surgery, School of Medicine, University of California-Davis, Davis, CA, United States., Ann-Marie Mallon, Colin McKerlie, Stephen A Murray, Lauryl M J Nutter, Helen Parkinson, John R Seavitt, Sara Wells, Rodney C Samaco, Elissa J Chesler, Damian Smedley, Luda Diatchenko, Kyle M Baumbauer, Erin E Young, Robert P Bonin, Silvia Mandillo, Jacqueline K White, and International Mouse Phenotyping Consortium.
    • The Jackson Laboratory, Bar Harbor, ME, United States.
    • Pain. 2022 Jun 1; 163 (6): 113911571139-1157.

    AbstractIdentifying the genetic determinants of pain is a scientific imperative given the magnitude of the global health burden that pain causes. Here, we report a genetic screen for nociception, performed under the auspices of the International Mouse Phenotyping Consortium. A biased set of 110 single-gene knockout mouse strains was screened for 1 or more nociception and hypersensitivity assays, including chemical nociception (formalin) and mechanical and thermal nociception (von Frey filaments and Hargreaves tests, respectively), with or without an inflammatory agent (complete Freund's adjuvant). We identified 13 single-gene knockout strains with altered nocifensive behavior in 1 or more assays. All these novel mouse models are openly available to the scientific community to study gene function. Two of the 13 genes (Gria1 and Htr3a) have been previously reported with nociception-related phenotypes in genetically engineered mouse strains and represent useful benchmarking standards. One of the 13 genes (Cnrip1) is known from human studies to play a role in pain modulation and the knockout mouse reported herein can be used to explore this function further. The remaining 10 genes (Abhd13, Alg6, BC048562, Cgnl1, Cp, Mmp16, Oxa1l, Tecpr2, Trim14, and Trim2) reveal novel pathways involved in nociception and may provide new knowledge to better understand genetic mechanisms of inflammatory pain and to serve as models for therapeutic target validation and drug development.Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.

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