title: 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.
abstract: 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.
authors.affiliation: Department of Veterinary Pathology, Freie Universität Berlin, Berlin, Germany.
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Erickson
authors.affiliation: Department of Medical Biochemistry, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Elisabeth E L
authors.initials: EE
authors.lastname: Nyström
authors.affiliation: Department of Veterinary Pathology, Freie Universität Berlin, Berlin, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Mundhenk
authors.affiliation: Department of Medical Biochemistry, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Liisa
authors.initials: L
authors.lastname: Arike
authors.affiliation: Medical Department, Division of Gastroenterology, Infectiology and Rheumatology-Charité, Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Glauben
authors.affiliation: Department of Microbiology and Hygiene, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Markus M
authors.initials: MM
authors.lastname: Heimesaat
authors.affiliation: Department of Microbiology and Hygiene, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: André
authors.initials: A
authors.lastname: Fischer
authors.affiliation: Department of Microbiology and Hygiene, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Bereswill
authors.affiliation: Department of Medical Biochemistry, University of Gothenburg, Gothenburg, Sweden.
authors.forename: George M H
authors.initials: GM
authors.lastname: Birchenough
authors.affiliation: Department of Veterinary Pathology, Freie Universität Berlin, Berlin, Germany.
authors.forename: Achim D
authors.initials: AD
authors.lastname: Gruber
authors.affiliation: Department of Medical Biochemistry, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Malin E V
authors.initials: ME
authors.lastname: Johansson
mesh_terms: D000818:Animals; D018118:Chloride Channels / Q000502:physiology*; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D003106:Colon / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D016264:Dextran Sulfate; D005243:Feces / Q000382:microbiology; D015870:Gene Expression; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D064307:Microbiota; D055262:Mucin-2 / Q000378:metabolism; D009093:Mucus / Q000378:metabolism*; D010539:Permeability; D012336:RNA, Ribosomal, 16S / Q000235:genetics
chemical_list: D018118:Chloride Channels; C116464:Clca3a1 protein, mouse; C524626:Muc2 protein, mouse; D055262:Mucin-2; D012336:RNA, Ribosomal, 16S; D016264:Dextran Sulfate