Natural cathepsin E deficiency in the immune system of C57BL/6J mice.
Cathepsin E is an aspartic endosomal proteinase, expressed at high levels in some epithelial and haemopoetic cells. The enzyme has been implicated in a variety of functions, including antigen processing. This study documents strain-specific variation in expression of cathepsin E in mice. The levels of cathepsin E protein and message are profoundly decreased in haemopoetic cells from C57BL/6J mice, compared to levels in 129S2/Sv or Balb/c. The deficiency is cell-type-specific, as protein levels in gut are not affected. Deficiency affects B cell, T cells, macrophages and dendritic cells. The low cathepsin E phenotype cosegregates with the C57BL/6J genotype in a panel of C57BL/6J x 129S2/Sv F2 mice. Analysis of the promoter region of cathepsin E reveals a polymorphism which destroys a previously described functional PU.1 transcription binding consensus sequence in the C57BL/6J genome. Antigen processing of ovalbumin by dendritic cells, which has previously been shown to require cathepsin E, is impaired in C57BL/6J-derived dendritic cells. C57BL/6J mice thus exhibit a profound tissue-specific deficiency in cathepsin E expression, which may have important implications for the immune phenotype of this mouse strain.
Tulone
Calogero
C
Division of Infection and Immunity, UCL, Windeyer Building, 46 Cleveland St., London, W1T 4JF, UK.
Tsang
Jhen
J
Prokopowicz
Zofia
Z
Grosvenor
Nicholas
N
Chain
Benny
B
D000818:Animals; D017951:Antigen Presentation; D001402:B-Lymphocytes / Q000276:immunology; D001483:Base Sequence; D015153:Blotting, Western; D002402:Cathepsin D / Q000235:genetics / Q000378:metabolism; D020059:Cathepsin E / Q000172:deficiency* / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D007107:Immune System / Q000502:physiology*; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D022423:Myeloid Cells / Q000276:immunology; D011401:Promoter Regions, Genetic / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D015534:Trans-Activators / Q000378:metabolism; D015533:Transcriptional Activation; D000099232:Proto-Oncogene Protein Spi-1
D002402:Cathepsin D; D020059:Cathepsin E; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1