title: Nlrp12 mutation causes C57BL/6J strain-specific defect in neutrophil recruitment.
abstract: The inbred mouse strain C57BL/6J is widely used in models of immunological and infectious diseases. Here we show that C57BL/6J mice have a defect in neutrophil recruitment to a range of inflammatory stimuli compared with the related C57BL/6N substrain. This immune perturbation is associated with a missense mutation in Nlrp12 in C57BL/6J mice. Both C57BL/6J and NLRP12-deficient mice have increased susceptibility to bacterial infection that correlates with defective neutrophil migration. C57BL/6J and NLRP12-deficient macrophages have impaired CXCL1 production and the neutrophil defect observed in C57BL/6J and NLRP12-deficient mice is rescued by restoration of macrophage NLRP12. These results demonstrate that C57BL/6J mice have a functional defect in NLRP12 and that macrophages require NLRP12 expression for effective recruitment of neutrophils to inflammatory sites.
authors: Inflammation Program, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA.|Interdisciplinary Program in Molecular and Cellular Biology, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA.
authors: Tyler K
authors: 0000-0002-6507-4989
authors: TK
authors: Ulland
authors: Inflammation Program, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA.|Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA.
authors: Nidhi
authors: N
authors: Jain
authors: Inflammation Program, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA.|Interdisciplinary Program in Immunology, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA.
authors: Emma E
authors: EE
authors: Hornick
authors: Inflammation Program, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA.|Interdisciplinary Program in Molecular and Cellular Biology, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA.|Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA.|Medical Scientist Training Program, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA.
authors: Eric I
authors: EI
authors: Elliott
authors: Interdisciplinary Program in Molecular and Cellular Biology, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA.|Medical Scientist Training Program, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA.
authors: Gwendolyn M
authors: GM
authors: Clay
authors: Inflammation Program, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA.
authors: Jeffrey J
authors: JJ
authors: Sadler
authors: Inflammation Program, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA.
authors: Kathleen A M
authors: KA
authors: Mills
authors: Inflammation Program, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA.|Interdisciplinary Program in Immunology, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA.
authors: Ann M
authors: AM
authors: Janowski
authors: Inflammation Program, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA.|Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA.
authors: A Paige Davis
authors: AP
authors: Volk
authors: Department of Biostatistics, University of Iowa College of Public Health, Iowa City, Iowa 52242, USA.
authors: Kai
authors: K
authors: Wang
authors: Interdisciplinary Program in Immunology, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA.|Medical Scientist Training Program, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA.|Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA.
authors: Kevin L
authors: KL
authors: Legge
authors: Department of Biochemistry, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA.|Protein Crystallography Facility, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA.
authors: Lokesh
authors: 0000-0002-3319-1902
authors: L
authors: Gakhar
authors: Molecular and Cellular Toxicology Section, Laboratory of Molecular Immunology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors: Mohammed
authors: M
authors: Bourdi
authors: Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA.
authors: Polly J
authors: PJ
authors: Ferguson
authors: Interdisciplinary Program in Molecular and Cellular Biology, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA.|Interdisciplinary Program in Immunology, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA.|Medical Scientist Training Program, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA.|Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA.|Veterans Affairs Medical Center, Iowa City, Iowa 52246, USA.|Department of Microbiology, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA.
authors: Mary E
authors: ME
authors: Wilson
authors: Inflammation Program, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA.|Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA.|Interdisciplinary Program in Immunology, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA.|Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA.
authors: Suzanne L
authors: SL
authors: Cassel
authors: Inflammation Program, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA.|Interdisciplinary Program in Molecular and Cellular Biology, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA.|Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA.|Interdisciplinary Program in Immunology, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA.|Medical Scientist Training Program, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA.|Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA.|Veterans Affairs Medical Center, Iowa City, Iowa 52246, USA.
authors: Fayyaz S
authors: FS
authors: Sutterwala
mesh_terms: D000818:Animals; D001483:Base Sequence; D002465:Cell Movement; D054360:Chemokine CXCL1 / Q000172:deficiency / Q000235:genetics* / Q000276:immunology; D004198:Disease Susceptibility; D005604:Francisella tularensis / Q000276:immunology; D015870:Gene Expression; D007113:Immunity, Innate; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency / Q000235:genetics* / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D009154:Mutation; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D016019:Survival Analysis; D014406:Tularemia / Q000235:genetics / Q000276:immunology* / Q000382:microbiology / Q000401:mortality
chemical_list: D054360:Chemokine CXCL1; C475895:Cxcl1 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; C553199:NLRP12 protein, mouse