7th Annual BMRP Investigator Meeting - Abstract

Protective Action of a Cysteine-Rich Mucin Domain on the Intestinal Mucosa in Experimental Colitis
 
Valérie Gouyer1-4, Hélène Valque3-5 and Jean-Luc Desseyn3,4,6,a
 
1INSERM U795; 2CHRU of Lille; 3IMPRT; 4University of Lille 2; 5EA3925; 6INSERM U837 (Lille, France)
 
CYS domains are nonglycosylated domains interspersed between heavily glycosylated domains in several secreted gel-forming mucins. The CYS domain is believed to act as crosslinker in the mucus gel and is likely an important determinant of the rheological properties –tight or loose net– of the gel. We hypothesized that this domain is a key molecule in the defence and the protection of the epithelia.

We created a mouse transgenic line that secreted in the lumen of the colon a string of 12 CYS domains. Histological sections showed a hypertrophy of the crypts, an increase of the number of Alcian blue/Periodic acid-Schiff (PAS)-stained cells in the upper half of the crypts and a loss of PAS-cells at the surface. Immunohistochemistry experiments showed a strong expression of the human CYS domain at the cell surface. Protection of the epithelium will be assessed (i) by challenging our transgenic mouse line with dextran sodium sulphate and (ii) by backcrossing our transgenic line with mice that develop spontaneous colitis.

aPrincipal Investigator