Role of mitochondria in intestinal epithelial cells

We aimed to study the role of mitochondria in intestinal epithelial cells by generating and analyzing mice with tamoxifen-inducible intestinal epithelial cell (IEC)-specific knockout of DARS2. DARS2 ablation caused severe mitochondrial dysfunction in IECs and resulted in suppression of epithelial cell proliferation and accumulation of lipids within large lipid droplets in enterocytes. To gain insight into the mechanism underlying the lipid processing defect, we used Lexogen 3' mRNA sequencing to compare the gene expression profiles of the proximal small intestine from mice with IEC-specific DARS2 knockout and control littermates at three days after tamoxifen induction, when the mice do not display yet lipid accumulation, and at seven days after tamoxifen induction, when enterocytes are filled with lipids. Overall design: 8-12 week-old DARS2tamIEC-KO and control mice received daily tamoxifen injections for five consecutive days and were sacrificed three or seven days after the last tamoxifen injection. A piece of a proximal small intestinal tissue was collected for RNA extraction and subsequent 3´ mRNA sequencing.