Altered distribution of aquaporin 5 and its C-terminal binding protein in the lacrimal glands of a mouse model for Sjögren's syndrome

Curr Eye Res. 2008 Aug;33(8):621-9. doi: 10.1080/02713680802262819.


Purpose: To investigate the distribution and expression of aquaporin 5 (AQP5) and its C-terminal binding protein in the apical membrane of the lacrimal glands (LGs) in a mouse model for Sjogren's syndrome (SS).

Methods: The LGs of NOD mice (mouse model for SS) and ICR mice (normal control) were homogenized and delivered into the affinity columns bound to synthetic AQP5 C-terminal peptide. The eluates were analyzed by electrophoresis and liquid chromatography mass spectrometry/mass spectrometry (LC-MS/MS) techniques.

Results: AQP5 from the NOD mice exhibited the capacity to bind a 21-kDa protein that was lacking in the ICR mice. Instead, ICR mouse expressed a 17-kDa AQP5 binding protein that was absent in LGs of SS. LC-MS/MS analysis revealed these respective proteins to be major urinary protein 4 (MUP4) and prolactin-inducible protein (PIP). The treatment of ICR mice with antisense PIP oligonucleotides decreased immunostaining of AQP5 in the apical membrane.

Conclusions: These observations suggest that the binding of PIP to the C-terminal portion of AQP5 may cause AQP5 to be transported to the apical membrane of LGs. Correction of the aberrant binding of PIP to the AQP5 C-terminus could normalize AQP5 trafficking to the apical membrane, leading to a treatment for patients with SS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohol Oxidoreductases / metabolism*
  • Animals
  • Aquaporin 5 / metabolism*
  • Blotting, Western
  • Carrier Proteins / metabolism*
  • Chromatography, Liquid
  • DNA-Binding Proteins / metabolism*
  • Disease Models, Animal*
  • Electrophoresis, Polyacrylamide Gel
  • Fluorescent Antibody Technique, Indirect
  • Lacrimal Apparatus / metabolism*
  • Male
  • Mice
  • Mice, Inbred ICR
  • Mice, Inbred NOD
  • Oligonucleotides, Antisense / pharmacology
  • Proteins / metabolism
  • Sjogren's Syndrome / metabolism*
  • Tandem Mass Spectrometry


  • Aqp5 protein, mouse
  • Aquaporin 5
  • Carrier Proteins
  • DNA-Binding Proteins
  • Oligonucleotides, Antisense
  • Proteins
  • major urinary proteins
  • Alcohol Oxidoreductases
  • C-terminal binding protein