Cloning and functional expression of the murine homologue of proteinase 3: implications for the design of murine models of vasculitis

FEBS Lett. 1997 May 19;408(2):187-90. doi: 10.1016/s0014-5793(97)00418-3.


Anti-neutrophil cytoplasmic autoantibodies recognizing conformational epitopes (c-ANCA) of proteinase 3 (PR3) from azurophil granules are a diagnostic hallmark in Wegener's granulomatosis (WG). Because a functional PR3 homologue has not been identified in rodents, it is difficult to assess immunopathological responses in rats or mice immunized with patients' derived c-ANCA or human PR3. Here we report the full length cDNA cloning and functional expression of murine PR3 in HMC-1 cells. Recombinant murine PR3 shows highly similar substrate specificities towards synthetic peptides and is inhibited by human alpha1-proteinase inhibitor like human PR3. However, neither human c-ANCA, rabbit sera nor mouse monoclonal antibodies to human PR3 recognize the murine homologue. Consequently, it is unlikely that disease observed in mice after immunization with c-ANCA or human PR3 is caused by pathogenic antibodies directed against mouse PR3. Recombinant human-mouse chimaeric variants will be a valuable new tool to localize the disease-specific immunodominant epitopes in human PR3.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Antineutrophil Cytoplasmic / immunology*
  • Antibody Specificity
  • Base Sequence
  • Cell Line
  • Cloning, Molecular
  • Disease Models, Animal
  • Epitopes / chemistry
  • Epitopes / immunology
  • Humans
  • Mast Cells / enzymology
  • Mice
  • Molecular Sequence Data
  • Myeloblastin
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / immunology
  • Recombinant Proteins / metabolism
  • Sequence Alignment
  • Serine Endopeptidases / chemistry
  • Serine Endopeptidases / genetics
  • Serine Endopeptidases / immunology*
  • Serine Endopeptidases / metabolism
  • Vasculitis / immunology*
  • alpha 1-Antitrypsin / pharmacology


  • Antibodies, Antineutrophil Cytoplasmic
  • Epitopes
  • Recombinant Proteins
  • alpha 1-Antitrypsin
  • Serine Endopeptidases
  • Myeloblastin