The Goblet Cell Protein Clca1 (Alias mClca3 or Gob-5) Is Not Required for
Intestinal Mucus Synthesis, Structure and Barrier Function in Naive or DSS-
Challenged Mice
The secreted, goblet cell-derived protein Clca1 (chloride channel regulator,
calcium-activated-1) has been linked to diseases with mucus overproduction,
including asthma and cystic fibrosis. In the intestine Clca1 is found in the
mucus with an abundance and expression pattern similar to Muc2, the major
structural mucus component. We hypothesized that Clca1 is required for the
synthesis, structure or barrier function of intestinal mucus and therefore
compared wild type and Clca1-deficient mice under naive and at various time
points of DSS (dextran sodium sulfate)-challenged conditions. The mucus
phenotype in Clca1-deficient compared to wild type mice was systematically
characterized by assessment of the mucus protein composition using proteomics,
immunofluorescence and expression analysis of selected mucin genes on mRNA
level. Mucus barrier integrity was assessed in-vivo by analysis of bacterial
penetration into the mucus and translocation into sentinel organs combined
analysis of the fecal microbiota and ex-vivo by assessment of mucus
penetrability using beads. All of these assays revealed no relevant
differences between wild type and Clca1-deficient mice under steady state or
DSS-challenged conditions in mouse colon. Clca1 is not required for mucus
synthesis, structure and barrier function in the murine colon