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.
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: Xiaochao Wei; Zhen Yang; Federico E Rey; Vanessa K Ridaura; Nicholas O Davidson; Jeffrey I Gordon; Clay F Semenkovich Journal: Cell Host Microbe Date: 2012-02-16 Impact factor: 21.023
Authors: R Steven Esworthy; Byung-Wook Kim; Yufeng Wang; Qiang Gao; James H Doroshow; Thomas L Leto; Fong-Fong Chu Journal: Free Radic Biol Med Date: 2013-10-01 Impact factor: 7.376
Authors: Peng Lu; Fabiana Bar-Yoseph; Liora Levi; Yael Lifshitz; Janneke Witte-Bouma; Adrianus C J M de Bruijn; Anita M Korteland-van Male; Johannes B van Goudoever; Ingrid B Renes Journal: PLoS One Date: 2013-06-12 Impact factor: 3.240
Authors: Peng Lu; Marie-Chantal Struijs; Jiaping Mei; Janneke Witte-Bouma; Anita M Korteland-van Male; Adrianus C J M de Bruijn; Johannes B van Goudoever; Ingrid B Renes Journal: PLoS One Date: 2013-10-23 Impact factor: 3.240