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


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 up-regulated 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.

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Fig. 1
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ATP-binding cassette sub-family B




Cytochrome P450


Inflammatory Bowel Diseases


Crohn’s Disease


Hypoxanthine phosphoribosyltransferase 1


Histological injury score


Insulin-like growth factor binding protein 7


Interferon gamma




Multidrug resistance


Neutrophil cytosolic factor 4


Regenerating islet-derived 3


Real time polymerase chain reaction


Single nucleotide polymorphism




Ulcerative Colitis


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Many thanks to Janice Rhodes and Hannah Smith (Crop and Food Research) for assistance with the mouse trial and Ric Broadhurst, Jason Peters, Bruce Sinclair and Kate Broadley (AgResearch Limited) for technical support throughout the study. The authors would also like to thank Julian Heyes and Juliet Sutherland (Crop and Food Research) for the valuable discussions and Katia Nones (Crop and Food Research) for proof-reading and editing the manuscript. This study is part of Nutrigenomics New Zealand, a collaboration between AgResearch, Crop & Food Research, HortResearch and The University of Auckland that is largely funded by the Foundation for Research, Science and Technology. Matthew Barnett is funded by a Foundation for Research, Science and Technology Postdoctoral Fellowship.

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Correspondence to C. A. Butts.

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Dommels, Y.E.M., Butts, C.A., Zhu, S. et al. Characterization of intestinal inflammation and identification of related gene expression changes in mdr1a−/− mice. Genes Nutr 2, 209–223 (2007) doi:10.1007/s12263-007-0051-4

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  • Colon
  • Gene expression
  • Intestinal Inflammation
  • Mice