Digestive Diseases and Sciences

, Volume 57, Issue 7, pp 1813–1821 | Cite as

Bin1 Attenuation Suppresses Experimental Colitis by Enforcing Intestinal Barrier Function

  • Mee Young Chang
  • Janette Boulden
  • M. Carmen Valenzano
  • Alejandro P. Soler
  • Alexander J. Muller
  • James M. Mullin
  • George C. Prendergast
Original Article



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.


This preclinical study aimed to evaluate an hypothesized role for the tumor suppressor gene Bin1 as a modifier of the severity of experimental colitis.


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.


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.


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.


IBD Colitis Inflammation Inflammatory cytokines Tight junctions Epithelial barrier 



We thank Gwen Guillard for tissue sectioning and histology. This work was supported in part by NCI R01 grants CA100123 and CA10954 with additional support from the Charlotte Geyer Foundation and the Lankenau Medical Center Foundation (G.C.P.). A.J.M. is the recipient of grants from the Lance Armstrong Foundation, the DoD Breast Cancer Research Program, and the State of Pennsylvania Department of Health (CURE/Tobacco Settlement Award). J.M.M is a recipient of a grant from the Sharpe-Strumia Foundation and the Prevent Cancer Foundation.

Conflict of interest


Supplementary material

10620_2012_2147_MOESM1_ESM.pdf (64 kb)
Supplemental Figure 1. Effect of Bin1 loss on immune cytokine expression. Serum was collected from mice administered 3 % DSS in drinking water for 7 days and the level of the immune cytokines indicated was determined by a cytometric bead array. The data represent the determination of at least three data points per sample (PDF 63 kb)


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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Mee Young Chang
    • 1
  • Janette Boulden
    • 1
  • M. Carmen Valenzano
    • 1
  • Alejandro P. Soler
    • 1
    • 2
  • Alexander J. Muller
    • 1
  • James M. Mullin
    • 1
  • George C. Prendergast
    • 1
    • 3
  1. 1.Lankenau Institute for Medical ResearchWynnewoodUSA
  2. 2.Richfield Laboratory of DermatopathologyCincinnatiUSA
  3. 3.Department of Pathology, Anatomy & Cell Biology, Jefferson Medical College and Kimmel Cancer CenterThomas Jefferson UniversityPhiladelphiaUSA

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