title: A differential gene expression study: Ptpn6 (SHP-1)-insufficiency leads to neutrophilic dermatosis-like disease (NDLD) in mice.
abstract: BACKGROUND
  Irradiated syngeneic wild-type mice developed the same neutrophilic dermatosis-like disease (NDLD) after adoptive transfer of bone marrow cells from Ptpn6(meb2/meb2) mutant mice.
  
  
  OBJECTIVE
  To analyze differentially expressed genes in the bone marrow of mice with NDLD to gain insight into the role of Ptpn6 in myelopoietic bone marrow pathology, and the mechanisms by which Ptpn6 insufficiency in the hematopoietic cells can lead to the development of skin lesions.
  
  
  METHODS
  As Ptpn6 is involved in a myriad of signaling pathways, we used a global approach with microarray technology for the first time to characterize changes in the bone marrow and skin of motheaten-type mice.
  
  
  RESULTS
  A total number of 1,511 probe sets in the bone marrow showed at least two-fold changes with FDR <0.05, of which 256 probe sets had over four-fold changes. A group of 63 genes in the bone marrow of NDLD mice had more than a 4-fold change with FDR <0.0001. From 503 genes encoding proteins with ITIM motif that binds to Ptpn6, 109 were up-regulated and 83 were down-regulated. We found that genes encoding hematopoietic receptors, neutrophil chemoattractants, Toll-like receptors (Tlr1, Tlr2 and Tlr4) and C-type lectin innate immunity receptors (Clec4e, Clec4d, Clec4n, Clec4a2 and Clec4a3) were significantly up-regulated in both NDLD bone marrow and skin. The Il1b gene was also significantly overexpressed in skin samples, confirming the importance of the IL-1/TLR pathway in the development of early skin inflammation in NDLD mice.
  
  
  CONCLUSIONS
  Our results suggest that innate immunity genes play a major role in development of neutrophilic dermatosis-like disease in mice.
authors.affiliation: Department of Dermatology, Rush University Medical Center, Chicago, IL 60612, USA. Electronic address: Andrew_B_Nesterovitch@rush.edu.
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Nesterovitch
authors.affiliation: Core Genomics Facility, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: Zarema
authors.initials: Z
authors.lastname: Arbieva
authors.affiliation: Department of Orthopedic Surgery (Section of Molecular Medicine), Biochemistry and Internal Medicine (Section of Rheumatology), Rush University Medical Center, Chicago, IL 60612, USA.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Toth
authors.affiliation: Department of Dermatology, Rush University Medical Center, Chicago, IL 60612, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Tharp
authors.affiliation: Department of Orthopedic Surgery (Section of Molecular Medicine), Biochemistry and Internal Medicine (Section of Rheumatology), Rush University Medical Center, Chicago, IL 60612, USA.
authors.forename: Tibor T
authors.initials: TT
authors.lastname: Glant
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D002454:Cell Differentiation; D020869:Gene Expression Profiling; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D053583:Interleukin-1beta / Q000378:metabolism*; D037181:Lectins, C-Type / Q000378:metabolism*; D051379:Mice; D009154:Mutation; D009504:Neutrophils / Q000276:immunology; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000235:genetics*; D017511:Pyoderma Gangrenosum / Q000235:genetics* / Q000276:immunology; D015398:Signal Transduction; D012867:Skin / Q000378:metabolism; D016463:Sweet Syndrome / Q000235:genetics* / Q000276:immunology; D051193:Toll-Like Receptors / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C587672:IL1B protein, mouse; D053583:Interleukin-1beta; D037181:Lectins, C-Type; D051193:Toll-Like Receptors; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; C509248:Ptpn6 protein, mouse
keywords: Autoinflammatory; Gene expression microarray; Motheaten; Neutrophilic dermatoses; Pyoderma gangrenosum; SHP-1