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

Abstract

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.

Nutrigenomics applied to an animal model of Inflammatory Bowel Diseases: Transcriptomic analysis of the effects of eicosapentaenoic acid- and arachidonic acid-enriched diets

“…In colonic tissue, to our knowledge, there is no report of ABCB4 gene expression in the literature. As in this study, chronic colonic inflammation as observed in IBD patients and in animal models of IBD can result in a down-regulation of other ABC genes, such as ABCB1A and ABCB1B [38][39][40] suggesting a dysregulation of the ABC transporters during inflammation. In contrast, PUFA-enriched diets resulted in an up-regulation of the ABCB4 gene and likely, in a more optimal lipid translocation.…”

Development of Cryptosporidium parvum-Induced Gastrointestinal Neoplasia in Severe Combined Immunodeficiency (SCID) Mice: Severity of Lesions Is Correlated with Infection Intensity

“…In 6/16 animals (37.5%) (mice nos. 7,8,15,16,24, and 32), lesions were detected in more than one organ with a maximum score of histologic severity of 11 in mouse no. 16 ( Table 1 ).…”

ADAMDEC1 Is a Metzincin Metalloprotease with Dampened Proteolytic Activity

“…It is expressed during differentiation of dendritic cells and is constitutively expressed in macrophages (1,12). Until now, ADAMDEC1 has primarily been studied on a transcriptional level, where it has been found differently regulated in a number of pathologies (13)(14)(15)(16)(17)(18).…”