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http://purl.uniprot.org/citations/23451046http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/23451046http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/23451046http://www.w3.org/2000/01/rdf-schema#comment"Roquin, an E3 ubiquitin ligase that localizes to cytosolic RNA granules, is involved in regulating mRNA stability and translation. Mice that have a M199R mutation in the Roquin protein (referred to as sanroque or Roquin(san/san) mice) develop autoimmune pathologies, although the extent to which these occur in the intestinal mucosa has not been determined. Here, we demonstrate that Roquin(san/san) mice reproducibly develop intestinal inflammation in the small intestine but not the colon. Similarly, mice generated in our laboratory in which the Roquin gene was disrupted by insertion of a gene trap cassette (Roquin(gt/gt) mice) had small intestinal inflammation that mimicked that of Roquin(san/san) mice. MLN cells in Roquin(san/san) mice consisted of activated proliferating T cells, and had increased numbers of CD44(hi) CD62L(lo) KLRG1(+) short-lived effector cells. Proportionally more small intestinal intraepithelial lymphocytes in Roquin(san/san) mice expressed the ICOS T cell activation marker. Of particular interest, small intestinal lamina propria lymphocytes in Roquin(san/san) mice consisted of a high proportion of Gr-1(+) T cells that included IL-17A(+) cells and CD8(+) IFN-γ(+) cells. Extensive cytokine dysregulation resulting in both over-expression and under-expression of chemotactic cytokines occurred in the ileum of Roquin(san/san) mice, the region most prone to the development of inflammation. These findings demonstrate that chronic inflammation ensues in the intestine following Roquin alteration either as a consequence of protein mutation or gene disruption, and they have implications for understanding how small intestinal inflammation is perpetuated in Crohn's disease (CD). Due to the paucity of animal models of CD-like pathophysiology in the small intestine, and because the primary gene/protein defects of the Roquin animal systems used here are well-defined, it will be possible to further elucidate the underlying genetic and molecular mechanisms that drive the disease process."xsd:string
http://purl.uniprot.org/citations/23451046http://purl.org/dc/terms/identifier"doi:10.1371/journal.pone.0056436"xsd:string
http://purl.uniprot.org/citations/23451046http://purl.org/dc/terms/identifier"doi:10.1371/journal.pone.0056436"xsd:string
http://purl.uniprot.org/citations/23451046http://purl.uniprot.org/core/author"Klein J.R."xsd:string
http://purl.uniprot.org/citations/23451046http://purl.uniprot.org/core/author"Klein J.R."xsd:string
http://purl.uniprot.org/citations/23451046http://purl.uniprot.org/core/author"Montufar-Solis D."xsd:string
http://purl.uniprot.org/citations/23451046http://purl.uniprot.org/core/author"Montufar-Solis D."xsd:string
http://purl.uniprot.org/citations/23451046http://purl.uniprot.org/core/author"Nakra N."xsd:string
http://purl.uniprot.org/citations/23451046http://purl.uniprot.org/core/author"Nakra N."xsd:string
http://purl.uniprot.org/citations/23451046http://purl.uniprot.org/core/author"Schaefer J.S."xsd:string
http://purl.uniprot.org/citations/23451046http://purl.uniprot.org/core/author"Schaefer J.S."xsd:string
http://purl.uniprot.org/citations/23451046http://purl.uniprot.org/core/author"Vigneswaran N."xsd:string
http://purl.uniprot.org/citations/23451046http://purl.uniprot.org/core/author"Vigneswaran N."xsd:string
http://purl.uniprot.org/citations/23451046http://purl.uniprot.org/core/date"2013"xsd:gYear
http://purl.uniprot.org/citations/23451046http://purl.uniprot.org/core/date"2013"xsd:gYear
http://purl.uniprot.org/citations/23451046http://purl.uniprot.org/core/name"PLoS ONE"xsd:string
http://purl.uniprot.org/citations/23451046http://purl.uniprot.org/core/name"PLoS ONE"xsd:string
http://purl.uniprot.org/citations/23451046http://purl.uniprot.org/core/pages"E56436"xsd:string
http://purl.uniprot.org/citations/23451046http://purl.uniprot.org/core/pages"E56436"xsd:string
http://purl.uniprot.org/citations/23451046http://purl.uniprot.org/core/title"Small intestine inflammation in Roquin-mutant and Roquin-deficient mice."xsd:string
http://purl.uniprot.org/citations/23451046http://purl.uniprot.org/core/title"Small intestine inflammation in Roquin-mutant and Roquin-deficient mice."xsd:string
http://purl.uniprot.org/citations/23451046http://purl.uniprot.org/core/volume"8"xsd:string
http://purl.uniprot.org/citations/23451046http://purl.uniprot.org/core/volume"8"xsd:string
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