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Identifying genetic determinants of inflammatory pain in mice using a large-scale gene-targeted screen.
Wotton, Janine M; Peterson, Emma; Flenniken, Ann M; Bains, Rasneer S; Veeraragavan, Surabi; Bower, Lynette R; Bubier, Jason A; Parisien, Marc; Bezginov, Alexandr; Haselimashhadi, Hamed; Mason, Jeremy; Moore, Michayla A; Stewart, Michelle E; Clary, Dave A; Delbarre, Daniel J; Anderson, Laura C; D'Souza, Abigail; Goodwin, Leslie O; Harrison, Mark E; Huang, Ziyue; Mckay, Matthew; Qu, Dawei; Santos, Luis; Srinivasan, Subhiksha; Urban, Rachel; Vukobradovic, Igor; Ward, Christopher S; Willett, Amelia M; Braun, Robert E; Brown, Steve D M; Dickinson, Mary E; Heaney, Jason D; Kumar, Vivek; Lloyd, K C Kent; Mallon, Ann-Marie; McKerlie, Colin; Murray, Stephen A; Nutter, Lauryl M J; Parkinson, Helen; Seavitt, John R; Wells, Sara; Samaco, Rodney C; Chesler, Elissa J; Smedley, Damian; Diatchenko, Luda; Baumbauer, Kyle M; Young, Erin E; Bonin, Robert P; Mandillo, Silvia; White, Jacqueline K.
Afiliación
  • Wotton JM; The Jackson Laboratory, Bar Harbor, ME, United States.
  • Peterson E; The Jackson Laboratory, Bar Harbor, ME, United States.
  • Flenniken AM; The Centre for Phenogenomics, Toronto, ON, Canada.
  • Bains RS; Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, ON, Canada.
  • Veeraragavan S; The Mary Lyon Centre, MRC Harwell Institute, Didcot, Oxfordshire, United Kingdom.
  • Bower LR; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, United States.
  • Bubier JA; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX, United States.
  • Parisien M; Mouse Biology Program, University of California-Davis, Davis, CA, United States.
  • Bezginov A; The Jackson Laboratory, Bar Harbor, ME, United States.
  • Haselimashhadi H; Department of Anesthesia, Faculty of Medicine, Faculty of Dentistry, McGill University, Genome Building, Montreal, QC, Canada.
  • Mason J; The Centre for Phenogenomics, Toronto, ON, Canada.
  • Moore MA; The Hospital for Sick Children, Toronto, ON, Canada.
  • Stewart ME; European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Hinxton, Cambridgeshire, United Kingdom.
  • Clary DA; European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Hinxton, Cambridgeshire, United Kingdom.
  • Delbarre DJ; The Jackson Laboratory, Bar Harbor, ME, United States.
  • Anderson LC; The Mary Lyon Centre, MRC Harwell Institute, Didcot, Oxfordshire, United Kingdom.
  • D'Souza A; Mouse Biology Program, University of California-Davis, Davis, CA, United States.
  • Goodwin LO; Mammalian Genetics Unit, MRC Harwell Institute, Didcot, Oxfordshire, United Kingdom.
  • Harrison ME; The Jackson Laboratory, Bar Harbor, ME, United States.
  • Huang Z; The Centre for Phenogenomics, Toronto, ON, Canada.
  • Mckay M; Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, ON, Canada.
  • Qu D; The Jackson Laboratory, Bar Harbor, ME, United States.
  • Santos L; The Mary Lyon Centre, MRC Harwell Institute, Didcot, Oxfordshire, United Kingdom.
  • Srinivasan S; The Centre for Phenogenomics, Toronto, ON, Canada.
  • Urban R; Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, ON, Canada.
  • Vukobradovic I; The Jackson Laboratory, Bar Harbor, ME, United States.
  • Ward CS; The Centre for Phenogenomics, Toronto, ON, Canada.
  • Willett AM; Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, ON, Canada.
  • Braun RE; Mammalian Genetics Unit, MRC Harwell Institute, Didcot, Oxfordshire, United Kingdom.
  • Brown SDM; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, United States.
  • Dickinson ME; The Jackson Laboratory, Bar Harbor, ME, United States.
  • Heaney JD; The Centre for Phenogenomics, Toronto, ON, Canada.
  • Kumar V; Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, ON, Canada.
  • Lloyd KCK; Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX, United States.
  • Mallon AM; The Jackson Laboratory, Bar Harbor, ME, United States.
  • McKerlie C; The Jackson Laboratory, Bar Harbor, ME, United States.
  • Murray SA; Mammalian Genetics Unit, MRC Harwell Institute, Didcot, Oxfordshire, United Kingdom.
  • Nutter LMJ; Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX, United States.
  • Parkinson H; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, United States.
  • Seavitt JR; The Jackson Laboratory, Bar Harbor, ME, United States.
  • Wells S; Mouse Biology Program, University of California-Davis, Davis, CA, United States.
  • Samaco RC; Department of Surgery, School of Medicine, University of California-Davis, Davis, CA, United States.
  • Chesler EJ; Mammalian Genetics Unit, MRC Harwell Institute, Didcot, Oxfordshire, United Kingdom.
  • Smedley D; Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, ON, Canada.
  • Diatchenko L; The Hospital for Sick Children, Toronto, ON, Canada.
  • Baumbauer KM; The Jackson Laboratory, Bar Harbor, ME, United States.
  • Young EE; The Centre for Phenogenomics, Toronto, ON, Canada.
  • Bonin RP; The Hospital for Sick Children, Toronto, ON, Canada.
  • Mandillo S; European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Hinxton, Cambridgeshire, United Kingdom.
  • White JK; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, United States.
Pain ; 163(6): 1139-1157, 2022 06 01.
Article en En | MEDLINE | ID: mdl-35552317
ABSTRACT: Identifying 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.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Dolor / Nocicepción Tipo de estudio: Guideline Límite: Animals Idioma: En Revista: Pain Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Dolor / Nocicepción Tipo de estudio: Guideline Límite: Animals Idioma: En Revista: Pain Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos