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Cloning and functional expression of the murine homologue of proteinase 3: implications for the design of murine models of vasculitis
Author(s) -
Jenne Dieter E.,
Fröhlich Leopold,
Hummel Amber M.,
Specks Ulrich
Publication year - 1997
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(97)00418-3
Subject(s) - cloning (programming) , proteinase 3 , microbiology and biotechnology , expression (computer science) , biology , chemistry , computational biology , immunology , autoantibody , computer science , antibody , programming language
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 α1‐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.