title: Colonic gene expression patterns of mucin Muc2 knockout mice reveal various phases in colitis development.
abstract: BACKGROUND
  Mucin Muc2 knockout (Muc2(-/-)) mice spontaneously develop colitis.
  
  
  METHODS
  To identify genes and biological responses which play a pivotal role during colitis development in Muc2(-/-) mice, gene expression profiles of colonic tissues from 2- and 4-week-old Muc2(-/-) and wildtype mice were determined using microarrays.
  
  
  RESULTS
  The majority of highly upregulated genes in 2-week-old as well as 4-week-old Muc2(-/-) mice were primarily involved in immune responses related to antigen processing/presentation, B-cell and T-cell receptor signaling, leukocyte transendothelial migration, and Jak-STAT signaling. Specifically, Muc2(-/-) mice expressed high levels of immunoglobulins, murine histocompatibility-2, proinflammatory cytokines, chemokines, and antimicrobial proteins. Additionally, in 4-week-old Muc2(-/-) mice, expression of genes involved in cell structure related pathways was significantly altered. Particularly, the tight junction-associated gene claudin-10 was upregulated, whereas claudin-1 and claudin-5 were downregulated. Furthermore, 4-week-old Muc2(-/-) mice showed increased expression of genes regulating cell growth in conjunction with increased crypt length and increased epithelial proliferation.
  
  
  CONCLUSIONS
  Muc2-deficiency leads to an active inflammatory response in 2- and 4-week-old Muc2(-/-) mice as demonstrated by the altered expression in immune response related genes. In addition, 4-week-old Muc2(-/-) mice also showed a decrease in epithelial barrier function and an increase in epithelial proliferation as indicated by, respectively, the altered expression in tight junction-related genes and upregulation of genes stimulating cell growth. Remarkably, upregulation of genes stimulating cell growth correlated with increased crypt length and increased epithelial proliferation in 4-week-old Muc2(-/-) mice. Together, these data demonstrate that there are distinct phases in colitis development in 2-4-week-old Muc2(-/-) mice.
authors: Laboratory of Pediatrics, Division Neonatology, Erasmus MC-Sophia, Rotterdam, The Netherlands.
authors: Peng
authors: P
authors: Lu
authors: Nanda
authors: N
authors: Burger-van Paassen
authors: Maria
authors: M
authors: van der Sluis
authors: Janneke
authors: J
authors: Witte-Bouma
authors: Jean-Pierre
authors: JP
authors: Kerckaert
authors: Johannes B
authors: JB
authors: van Goudoever
authors: Isabelle
authors: I
authors: Van Seuningen
authors: Ingrid B
authors: IB
authors: Renes
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D003092:Colitis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D003106:Colon / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D020869:Gene Expression Profiling; D007124:Immunoenzyme Techniques; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D055262:Mucin-2 / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D015415:Biomarkers; C524626:Muc2 protein, mouse; D055262:Mucin-2; D012333:RNA, Messenger