title: Cappuccino mutation in an autoimmune-prone strain of mice suggests a role of platelet function in the progression of immune complex crescentic glomerulonephritis.
abstract: OBJECTIVE
  Crescent formation in the renal glomerulus is a typical manifestation of progressive glomerulopathy associated with fatal renal failure; therefore, its prevention is of clinical importance. Little is known about the pathogenic mechanism for crescent formation. This study was undertaken in an attempt to identify the events that are critical for crescent formation in immune complex crescentic glomerulonephritis (CGN) by analyzing a novel mutant strain of mice.
  
  
  METHODS
  A spontaneous mutant strain of mice was isolated from the autoimmune-prone strain EOD, which stably develops fatal CGN. The mutant phenotypes were assessed histopathologically, hematologically, and immunologically. The mutation was searched for with positional cloning using microsatellite markers.
  
  
  RESULTS
  Compared with wild-type EOD (WT-EOD) mice, mutant EOD (mut-EOD) mice showed marked improvement in CGN in conjunction with an improvement in spontaneous mortality. In WT-EOD mice, an inverse correlation between blood urea nitrogen concentration and blood platelet count and massive accumulation of platelets in the glomerulus were evident, suggesting that an accumulation of platelets in the glomerulus contributes to the progression of CGN. The mutant platelets showed an abnormal aggregation in response to collagen and thrombin, associated with a bleeding tendency in mut-EOD mice. Genetic analysis revealed a deleterious mutation in the cappuccino gene (cno), which encodes a protein that belongs to a complex called the biogenesis of lysosome-related organelle complex 1 and is profoundly involved in platelet function. Morphologic examination revealed a partial defect in dense body formation in the delta-granule of platelets.
  
  
  CONCLUSIONS
  The present findings suggest that platelet functions have a critical role in crescent formation in autoimmune GN.
authors.affiliation: Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Minako
authors.initials: M
authors.lastname: Yoshida
authors.forename: Kan
authors.initials: K
authors.lastname: Saiga
authors.forename: Takaaki
authors.initials: T
authors.lastname: Hato
authors.forename: Shoko
authors.initials: S
authors.lastname: Iwaki
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Niiya
authors.forename: Norimasa
authors.initials: N
authors.lastname: Arita
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Komori
authors.forename: Takahito
authors.initials: T
authors.lastname: Tsubaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Furukawa
authors.forename: Miho
authors.initials: M
authors.lastname: Terada
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Maeyama
authors.forename: Kyuichi
authors.initials: K
authors.lastname: Nemoto
authors.forename: Masato
authors.initials: M
authors.lastname: Nose
authors.forename: Masao
authors.initials: M
authors.lastname: Ono
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics; D001772:Blood Cell Count; D001792:Blood Platelets / Q000502:physiology*; D001806:Blood Urea Nitrogen; D017931:DNA Primers; D005921:Glomerulonephritis / Q000097:blood / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D015151:Immunoblotting; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D010641:Phenotype; D033921:Vesicular Transport Proteins / Q000235:genetics*
chemical_list: C475462:Bloc1s4 protein, mouse; D017931:DNA Primers; D033921:Vesicular Transport Proteins