title: Sialoadhesin deficiency does not influence the severity of lupus nephritis in New Zealand black x New Zealand white F1 mice.
abstract: BACKGROUND
  Systemic lupus erythematosus (SLE) is a chronic inflammatory condition with multisystem involvement. One of the key features of the disease is the upregulation of type I interferons, resulting in the so-called "interferon signature". Recent flow cytometric and transcriptomic studies identified Sialoadhesin (Sn, CD169) as an important interferon-induced blood monocyte biomarker in diseased patients. To investigate a potential causative role of Sn in SLE, we generated NZBWF1 (New Zealand Black x New Zealand White F1) mice lacking Sn and compared onset and progression of disease with NZBWF1 expressing normal levels of Sn.
  
  
  METHODS
  Sn expression in renal tissues of pre-diseased and diseased NZBWF1 mice was evaluated by Quantitative real time PCR (QPCR) and immunohistochemistry. Sn-/- NZBWF1 mice were generated by speed congenics. Disease severity of Sn+/+ and Sn-/- NZBWF1 mice was assessed by serum immunoassays, flow cytometry, light microscopy and immunohistochemistry.
  
  
  RESULTS
  Renal tissues from proteinuric NZBWF1 mice exhibited a significant upregulation of Sn mRNA and protein expression following disease onset. Further immunohistochemical analysis showed that Sn+ macrophages assumed a distinct periglomerular distribution and, unlike CD68+ macrophages, were not present within the glomeruli. Analysis of disease severity in Sn-/- and Sn+/+ NZBWF1 mice revealed no significant differences in the disease progression between the two groups although Sn-deficient mice showed a more rapid onset of proteinuria.
  
  
  CONCLUSIONS
  These data confirm a positive correlation of Sn with disease activity. However, Sn deficiency does not have a significant effect on the severity and progression of lupus nephritis in the NZBWF1 mouse model.
authors.forename: Dana
authors.initials: D
authors.lastname: Kidder
authors.forename: Hannah E
authors.initials: HE
authors.lastname: Richards
authors.forename: Paul A
authors.initials: PA
authors.lastname: Lyons
authors.forename: Paul R
authors.initials: PR
authors.lastname: Crocker
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005434:Flow Cytometry; D007150:Immunohistochemistry; D008181:Lupus Nephritis / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D060888:Real-Time Polymerase Chain Reaction; D063267:Sialic Acid Binding Ig-like Lectin 1 / Q000172:deficiency / Q000378:metabolism*
chemical_list: D063267:Sialic Acid Binding Ig-like Lectin 1