Muc2-deficient mice spontaneously develop colitis, indicating that MUC2 is critical for colonic protection.
OBJECTIVE
Expression of mucin MUC2, the structural component of the colonic mucus layer, is lowered in inflammatory bowel disease. Our aim was to obtain insight in the role of Muc2 in epithelial protection.


METHODS
Muc2 knockout (Muc2(-/-)) and Muc2 heterozygous (Muc2(+/-)) mice were characterized and challenged by a colitis-inducing agent, dextran sulfate sodium (DSS). We monitored clinical symptoms, intestinal morphology, and differences in intestine-specific protein and messenger RNA levels.


RESULTS
The Muc2(-/-) mice showed clinical signs of colitis (as of 5 weeks), aggravating as the mice aged. Microscopic analysis of the colon of Muc2(-/-) mice showed mucosal thickening, increased proliferation, and superficial erosions. Colonic goblet cells in the Muc2(-/-) mice were negative for Muc2, but trefoil factor 3 was still detectable. In Muc2(-/-) mice, transient de novo expression of Muc6 messenger RNA was observed in the distal colon. On day 2 of DSS treatment, the histologic damage was more severe in Muc2(+/-) versus wild-type (Muc2(+/+)) mice, but the disease activity index was not yet different. By day 7, the disease activity index and histologic score were significantly elevated in Muc2(+/-) versus Muc2(+/+) mice. The disease activity index of the Muc2(-/-) mice was higher (versus both Muc2(+/+) and Muc2(+/-) mice) throughout DSS treatment. The histologic damage in the DSS-treated Muc2(-/-) mice was different compared with Muc2(+/+) and Muc2(+/-) mice, with many crypt abscesses instead of mucosal ulcerations.


CONCLUSIONS
This study shows that Muc2 deficiency leads to inflammation of the colon and contributes to the onset and perpetuation of experimental colitis.
Van der Sluis
Maria
M
Division of Neonatology, Department of Pediatrics, Erasmus MC and Sophia Children's Hospital, Rotterdam, The Netherlands.
De Koning
Barbara A E
BA
De Bruijn
Adrianus C J M
AC
Velcich
Anna
A
Meijerink
Jules P P
JP
Van Goudoever
Johannes B
JB
Büller
Hans A
HA
Dekker
Jan
J
Van Seuningen
Isabelle
I
Renes
Ingrid B
IB
Einerhand
Alexandra W C
AW
D000818:Animals; D003092:Colitis / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D016264:Dextran Sulfate / Q000627:therapeutic use; D004195:Disease Models, Animal; D015870:Gene Expression; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051379:Mice; D055262:Mucin-2; D009077:Mucins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D010952:Plasma Substitutes / Q000627:therapeutic use; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics
C524626:Muc2 protein, mouse; D055262:Mucin-2; D009077:Mucins; D010952:Plasma Substitutes; D012333:RNA, Messenger; D016264:Dextran Sulfate