title: Bin1 attenuation suppresses experimental colitis by enforcing intestinal barrier function.
abstract: BACKGROUND
  Inflammatory bowel disease (IBD) is associated with defects in intestinal barriers that rely upon cellular tight junctions. Thus, identifying genes that could be targeted to enforce tight junctions and improve barrier function may lead to new treatment strategies for IBD.
  
  
  OBJECTIVE
  This preclinical study aimed to evaluate an hypothesized role for the tumor suppressor gene Bin1 as a modifier of the severity of experimental colitis.
  
  
  METHODS
  We ablated the Bin1 gene in a mosaic mouse model to evaluate its effects on experimental colitis and intestinal barrier function. Gross pathology, histology and inflammatory cytokine expression patterns were characterized and ex vivo physiology determinations were conducted to evaluate barrier function in intact colon tissue.
  
  
  RESULTS
  Bin1 attenuation limited experimental colitis in a sexually dimorphic manner with stronger protection in female subjects. Colitis suppression was associated with an increase in basal transepithelial electrical resistance (TER) and a decrease in paracellular transepithelial flux, compared to control wild-type animals. In contrast, Bin1 attenuation did not affect short circuit current, nor did it alter the epithelial barrier response to non-inflammatory permeability enhancers in the absence of inflammatory stimuli.
  
  
  CONCLUSIONS
  Bin1 is a genetic modifier of experimental colitis that controls the paracellular pathway of transcellular ion transport regulated by cellular tight junctions. Our findings offer a preclinical validation of Bin1 as a novel therapeutic target for IBD treatment.
authors.affiliation: Lankenau Institute for Medical Research, Wynnewood, PA 19096, USA.
authors.forename: Mee Young
authors.initials: MY
authors.lastname: Chang
authors.forename: Janette
authors.initials: J
authors.lastname: Boulden
authors.forename: M Carmen
authors.initials: MC
authors.lastname: Valenzano
authors.forename: Alejandro P
authors.initials: AP
authors.lastname: Soler
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Muller
authors.forename: James M
authors.initials: JM
authors.lastname: Mullin
authors.forename: George C
authors.initials: GC
authors.lastname: Prendergast
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D000818:Animals; D002463:Cell Membrane Permeability / Q000502:physiology*; D003092:Colitis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D016264:Dextran Sulfate / Q000009:adverse effects; D004195:Disease Models, Animal; D005260:Female; D007413:Intestinal Mucosa / Q000473:pathology / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D012720:Severity of Illness Index; D012727:Sex Characteristics; D019108:Tight Junctions / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C109221:Bin1 protein, mouse; D009419:Nerve Tissue Proteins; D025521:Tumor Suppressor Proteins; D016264:Dextran Sulfate