Increases in goblet cell number have been found in quiescent Crohn��s disease epithelium in contrast to a number of studies that show decreased goblet cell numbers in active Crohn��s disease and in ulcerative colitis,,. The goal of this study was to determine how goblet cell and mucus layer structure and function are altered in aganglionic colon from mice and humans. The overall aim of this study was to investigate changes to the colonic epithelium in the setting of congenital aganglionosis that may suggest possible etiologies for HAEC. A number of theories have emerged to explain the pathogenesis of HAEC. As with other inflammatory bowel conditions such as Crohn��s disease and ulcerative colitis, these theories have primarily focused on defects in colonic barrier function, innate immunity and the microbial milieu. The occurrence of enterocolitis both in HSCR patients and in mouse models of colonic aganglionosis suggest that there are fundamental changes to colonic structure and function that occur either in conjunction with defective neural crest migration or that result from the Olomoucine absence of enteric neuronal or glial function in the mucosa and submucosa. We obtained biopsy tissue from HSCR patients with minimal or no inflammation to see if there were obvious structural changes associated with aganglionosis. A common feature of the human tissues was increased numbers of goblet cells. Although the mean ages of the HSCR and control patients were similar, given the range of ages and clinical conditions in the patient biopsies we wanted to investigate possible epithelial differences without confounding by developmental or condition-specific changes. The mucus layer overlying the colonic epithelium has multiple functional roles, including providing an initial barrier to pathogens, altering selection pressures on commensal microbiota and lubrication of intestinal contents. The layer itself resembles a mesh of mucin glycoproteins, and anti-bacterial and signaling proteins within an aqueous environment. The alterations in goblet cell number and function found in mutant mice appear to produce a significantly different mucus layer environment, as shown by the altered diffusivity of 200 nm particles found in the particle tracking studies. These changes may be due to altered macro-scale viscoelastic properties and/or nano-scale changes in mucin interactions resulting in a reduced effective mesh pore size. Alternatively, the changes may reflect altered interaction between mucus proteins and the carboxylate surface groups of the particles. Our previous studies have shown significant alterations in the commensal PA 452 milieu in aganglionic colon, which we speculate may be related to the altered epithelial and goblet cell proliferation and differentiation and subsequent altered mucus environment found in this study.