title: Comparison of cellular location and expression of Plakophilin-2 in epidermal cells from nonlesional atopic skin and healthy skin in German shepherd dogs.
abstract: BACKGROUND
  Canine atopic dermatitis (CAD) is an inflammatory and pruritic allergic skin disease caused by interactions between genetic and environmental factors. Previously, a genome-wide significant risk locus on canine chromosome 27 for CAD was identified in German shepherd dogs (GSDs) and Plakophilin-2 (PKP2) was defined as the top candidate gene. PKP2 constitutes a crucial component of desmosomes and also is important in signalling, metabolic and transcriptional activities.
  
  
  OBJECTIVE
  The main objective was to evaluate the role of PKP2 in CAD by investigating PKP2 expression and desmosome structure in nonlesional skin from CAD-affected (carrying the top GWAS SNP risk allele) and healthy GSDs. We also aimed at defining the cell types in the skin that express PKP2 and its intracellular location.
  
  
  METHODS
  Skin biopsies were collected from nine CAD-affected and five control GSDs. The biopsies were frozen for immunofluorescence and fixed for electron microscopy immunolabelling and morphology.
  
  
  RESULTS
  We observed the novel finding of PKP2 expression in dendritic cells and T cells in dog skin. Moreover, we detected that PKP2 was more evenly expressed within keratinocytes compared to its desmosomal binding-partner plakoglobin. PKP2 protein was located in the nucleus and on keratin filaments attached to desmosomes. No difference in PKP2 abundance between CAD cases and controls was observed.
  
  
  CONCLUSIONS
  Plakophilin-2 protein in dog skin is expressed in both epithelial and immune cells; based on its subcellular location its functional role is implicated in both nuclear and structural processes.
authors.affiliation: Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, BMC, Uppsala University, Box 582, SE-75123, Uppsala, Sweden.|Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, Box 7023, SE-75007, Uppsala, Sweden.
authors.forename: Brita
authors.initials: B
authors.lastname: Ardesjö-Lundgren
authors.affiliation: Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, BMC, Uppsala University, Box 582, SE-75123, Uppsala, Sweden.|Neuroimmunology Unit, Centrum for Molecular Medicine, Department of Clinical Neuroscience, Karolinska Institutet, 17176, Stockholm, Sweden.
authors.forename: Katarina
authors.initials: K
authors.lastname: Tengvall
authors.affiliation: Department of Clinical Sciences, Swedish University of Agricultural Sciences, Box 7054, SE-75007, Uppsala, Sweden.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Bergvall
authors.affiliation: Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, BMC, Uppsala University, Box 582, SE-75123, Uppsala, Sweden.
authors.forename: Fabiana H G
authors.initials: FHG
authors.lastname: Farias
authors.affiliation: Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, Box 7011, SE-75007, Uppsala, Sweden.
authors.forename: Liya
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Clinical Sciences, Swedish University of Agricultural Sciences, Box 7054, SE-75007, Uppsala, Sweden.
authors.forename: Åke
authors.initials: Å
authors.lastname: Hedhammar
authors.affiliation: Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, BMC, Uppsala University, Box 582, SE-75123, Uppsala, Sweden.|Broad Institute of MIT and Harvard, 415 Main St, Cambridge, MA, 02142, USA.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Lindblad-Toh
authors.affiliation: Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, Box 7023, SE-75007, Uppsala, Sweden.
authors.forename: Göran
authors.initials: G
authors.lastname: Andersson
mesh_terms: D000818:Animals; D001706:Biopsy / Q000662:veterinary; D016022:Case-Control Studies; D003876:Dermatitis, Atopic / Q000378:metabolism / Q000662:veterinary*; D004283:Dog Diseases / Q000378:metabolism*; D004285:Dogs; D000078404:Epidermal Cells; D004817:Epidermis / Q000737:chemistry; D005260:Female; D008297:Male; D016253:Microscopy, Immunoelectron / Q000662:veterinary; D051191:Plakophilins / Q000032:analysis* / Q000378:metabolism; D012867:Skin / Q000737:chemistry / Q000378:metabolism*
chemical_list: D051191:Plakophilins