Characterization of intestinal inflammation and identification of related gene expression changes in mdr1a-/- mice

被引:70
作者
Dommels, Y. E. M. [1 ]
Butts, C. A. [1 ]
Zhu, S. [2 ]
Davy, M. [3 ]
Martell, S. [1 ]
Hedderley, D. [1 ]
Barnett, M. P. G. [4 ]
McNabb, W. C. [4 ]
Roy, N. C. [4 ]
机构
[1] Crop & Food Res, Palmertson N 4442, New Zealand
[2] Univ Auckland, Auckland 1142, New Zealand
[3] HortRes, Auckland 1142, New Zealand
[4] AgResearch Ltd, Food & Hlth Grp, Metab & Microbiol, Palmerston North 4442, New Zealand
关键词
colon; gene expression; intestinal inflammation; mice;
D O I
10.1007/s12263-007-0051-4
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Multidrug resistance targeted mutation (mdr1a(-/-)) mice spontaneously develop intestinal inflammation. The aim of this study was to further characterize the intestinal inflammation in mdr1a(-/-) mice. Intestinal samples were collected to measure inflammation and gene expression changes over time. The first signs of inflammation occurred around 16 weeks of age and most mdr1a(-/-) mice developed inflammation between 16 and 27 weeks of age. The total histological injury score was the highest in the colon. The inflammatory lesions were transmural and discontinuous, revealing similarities to human inflammatory bowel diseases (IBD). Genes involved in inflammatory response pathways were upregulated whereas genes involved in biotransformation and transport were down-regulated in colonic epithelial cell scrapings of inflamed mdra1(-/-) mice at 25 weeks of age compared to non-inflamed FVB mice. These results show overlap to human IBD and strengthen the use of this in vivo model to study human IBD. The anti-inflammatory regenerating islet-derived genes were expressed at a lower level during inflammation initiation in non-inflamed colonic epithelial cell scrapings of mdr1a(-/-) mice at 12 weeks of age. This result suggests that an insufficiently suppressed immune response could be crucial to the initiation and development of intestinal inflammation in mdr1a(-/-) mice.
引用
收藏
页码:209 / 223
页数:15
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