title: Gene expression analysis detected a low expression level of C1s gene in ICR-derived glomerulonephritis (ICGN) mice.
abstract: BACKGROUND
  ICR-derived glomerulonephritis (ICGN) strain is a novel inbred strain of mice with a hereditary nephrotic syndrome. Deletion mutation of tensin 2 (Tns2), a focal adhesion molecule, has been suggested to be responsible for nephrotic syndrome in ICGN mice; however, the existence of other associative factors has been suggested.
  
  
  RESULTS
  To identify additional associative factors and to better understand the onset mechanism of nephrotic syndrome in ICGN mice, we conducted a comprehensive gene expression analysis using DNA microarray. Immune-related pathways were markedly altered in ICGN mice kidney as compared with ICR mice. Furthermore, the gene expression level of complement component 1, s subcomponent (C1s), whose human homologue has been reported to associate with lupus nephritis, was markedly low in ICGN mouse kidney. Real-time quantitative reverse transcription-polymerase chain reaction confirmed a low expression level of C1s in ICGN mouse liver where the C1s protein is mainly synthesized. A high serum level of anti-dsDNA antibody and deposits of immune complexes were also detected in ICGN mice by enzyme-linked immunosorbent assay and immunohistochemical analyses, respectively.
  
  
  CONCLUSIONS
  Our results suggest that the immune system, especially the complement system, is associated with nephrotic syndrome in ICGN mice. We identified a low expression level of C1s gene as an additional associative factor for nephrotic syndrome in ICGN mice. Further studies are needed to elucidate the role of the complement system in the onset of nephrotic syndrome in ICGN mice.
authors.affiliation: Drug Safety Research Laboratories, Astellas Pharma Inc., Osaka, Japan.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Tamura
authors.forename: Kozue
authors.initials: K
authors.lastname: Uchio-Yamada
authors.forename: Noboru
authors.initials: N
authors.lastname: Manabe
authors.forename: Takahisa
authors.initials: T
authors.lastname: Noto
authors.forename: Rika
authors.initials: R
authors.lastname: Hirota
authors.forename: Akira
authors.initials: A
authors.lastname: Unami
authors.forename: Masahiro
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Miyamae
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood / Q000276:immunology; D003173:Complement C1s / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005921:Glomerulonephritis / Q000097:blood / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008181:Lupus Nephritis / Q000235:genetics; D051379:Mice; D008813:Mice, Inbred ICR; D009404:Nephrotic Syndrome / Q000097:blood / Q000235:genetics* / Q000276:immunology; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D059467:Transcriptome
chemical_list: D000974:Antibodies, Antinuclear; D003173:Complement C1s