title: Reduced mucin sulfonation and impaired intestinal barrier function in the hyposulfataemic NaS1 null mouse.
abstract: OBJECTIVE
  Sulfate (SO(4)(2-)) is an abundant component of intestinal mucins and its content is decreased in certain gastrointestinal diseases, including inflammatory bowel disease. In this study, the hyposulfataemic NaS1 sulfate transporter null (Nas1(-/-)) mice were used to investigate the physiological consequences of disturbed sulfate homeostasis on (1) intestinal sulfomucin content and mRNA expression; (2) intestinal permeability and proliferation; (3) dextran sulfate sodium (DSS)-induced colitis; and (4) intestinal barrier function against the bacterial pathogen, Campylobacter jejuni.
  
  
  METHODS
  Intestinal sulfomucins and sialomucins were detected by high iron diamine staining, permeability was assessed by fluorescein isothiocyanate (FITC)-dextran uptake, and proliferation was assessed by 5-bromodeoxyuridine (BrdU) incorporation. Nas1(-/-) and wild-type (Nas1(+/+)) mice received DSS in drinking water, and intestinal damage was assessed by histological, clinical and haematological measurements. Mice were orally inoculated with C jejuni, and intestinal and systemic infection was assessed. Ileal mRNA expression profiles of Nas1(-/-) and Nas1(+/+) mice were determined by cDNA microarrays and validated by quantitative real-time PCR.
  
  
  RESULTS
  Nas1(-/-) mice exhibited reduced intestinal sulfomucin content, enhanced intestinal permeability and DSS-induced colitis, and developed systemic infections when challenged orally with C jejuni. The transcriptional profile of 41 genes was altered in Nas1(-/-) mice, with the most upregulated gene being pancreatic lipase-related protein 2 and the most downregulated gene being carbonic anhydrase 1 (Car1).
  
  
  CONCLUSIONS
  Sulfate homeostasis is essential for maintaining a normal intestinal metabolic state, and hyposulfataemia leads to reduced intestinal sulfomucin content, enhanced susceptibility to toxin-induced colitis and impaired intestinal barrier to bacterial infection.
authors.affiliation: School of Biomedical Sciences, University of Queensland, St Lucia, QLD 4072, Australia.
authors.forename: P A
authors.initials: PA
authors.lastname: Dawson
authors.forename: S
authors.initials: S
authors.lastname: Huxley
authors.forename: B
authors.initials: B
authors.lastname: Gardiner
authors.forename: T
authors.initials: T
authors.lastname: Tran
authors.forename: J L
authors.initials: JL
authors.lastname: McAuley
authors.forename: S
authors.initials: S
authors.lastname: Grimmond
authors.forename: M A
authors.initials: MA
authors.lastname: McGuckin
authors.forename: D
authors.initials: D
authors.lastname: Markovich
mesh_terms: D000818:Animals; D002169:Campylobacter Infections / Q000382:microbiology; D016123:Campylobacter jejuni / Q000302:isolation & purification; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism* / Q000382:microbiology; D007150:Immunohistochemistry; D007408:Intestinal Absorption / Q000187:drug effects; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000382:microbiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009077:Mucins / Q000378:metabolism*; D013997:Time Factors
chemical_list: D009077:Mucins; C012564:sulfomucin