Heterogeneity in expression and subcellular localization of claudins 2, 3, 4, and 5 in the rat liver, pancreas, and gut

Gastroenterology. 2001 Feb;120(2):411-22. doi: 10.1053/gast.2001.21736.


Background & aims: Paracellular transport varies widely among epithelia of the gastrointestinal tract. We determined whether members of the claudin family of tight junction proteins are differentially expressed consistent with a potential role in creating these variable properties.

Methods: Rabbit polyclonal antibodies were produced against peptides from claudins 2 through 5. The distribution of individual claudins was detected by immunoblotting, and their cell type and subcellular localization were determined by immunofluorescence on cryosections of rat liver, pancreas, stomach, and small and large intestine.

Results: All antibodies detected single bands of the expected size on immunoblots and were monospecific based on peptide competition studies. Immunoblotting detected strong differences among tissues in the expression level of each claudin. Immunolocalization confirmed these differences and revealed striking variations in expression patterns. In the liver, claudin 2 shows a lobular gradient increasing from periportal to pericentral hepatocytes, claudin 3 is uniformly expressed, claudin 4 is absent, and claudin 5 is only expressed in endothelial junctions. In the pancreas, claudin 2 is only detected in junctions of the duct epithelia, claudin 5 only in junctions of acinar cells, whereas claudin 3 and 4 are in both. Among differences in the gut are a crypt-to-villus decrease in claudin 2, a highly restricted expression of claudin 4 to colonic surface cells, and the finding that some claudins can be junctional, lateral, or show a gradient in junctional vs. lateral localization along the crypt-to-villus surface axis.

Conclusions: Claudins have very different expression patterns among and within gastrointestinal tissues. We propose these patterns underlie differences in paracellular permeability properties, such as electrical resistance and ion selectivity that would complement known differences in transcellular transport.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibody Specificity
  • Claudin-3
  • Claudin-4
  • Claudin-5
  • Claudins
  • Gene Expression / physiology
  • Genetic Heterogeneity*
  • Intestines / chemistry
  • Intestines / physiology*
  • Liver / chemistry
  • Liver / physiology*
  • Male
  • Membrane Proteins / analysis
  • Membrane Proteins / genetics*
  • Membrane Proteins / immunology
  • Molecular Sequence Data
  • Occludin
  • Pancreas / chemistry
  • Pancreas / physiology*
  • Phosphoproteins / analysis
  • Phosphoproteins / immunology
  • Rats
  • Rats, Sprague-Dawley
  • Tight Junctions / chemistry
  • Tight Junctions / physiology
  • Zonula Occludens-1 Protein


  • CLDN2 protein, human
  • CLDN3 protein, human
  • CLDN4 protein, human
  • Claudin-3
  • Claudin-4
  • Claudin-5
  • Claudins
  • Cldn2 protein, rat
  • Cldn3 protein, mouse
  • Cldn3 protein, rat
  • Cldn4 protein, mouse
  • Cldn5 protein, mouse
  • Cldn5 protein, rat
  • Membrane Proteins
  • OCLN protein, human
  • Occludin
  • Ocln protein, mouse
  • Ocln protein, rat
  • Phosphoproteins
  • TJP1 protein, human
  • Tjp1 protein, mouse
  • Tjp1 protein, rat
  • Zonula Occludens-1 Protein