Serca2 deletion in the mouse adult Bmi1+ compartment induces a lethal phenotype involving a severe gastric dysfunction

Figure 4 Serca2 deletion in the intestinal epithelium provokes a fulminant lethal phenotype. A: Expression analysis (real-time quantitative polymerase chain reaction) of a panel of relevant genes involved endoplasmic reticulum stress in total duodenum tissue isolated in parallel from control (n = 3, each); DSerca2^Bmi1homo (5 days; n = 3, each) and DSerca2^Bmi1homo (7 days; n = 2, each) mice. All data were normalized to levels of the housekeeping gene Hprt; B: Electron microscopy analysis of microvilli length in DSerca2^Bmi1homo compared with control mice [5 days-post-tamoxifen (Tx)]. Representative images (50000 ×) are shown and representative example, microvilli are indicated with an orange line, with the estimated length in μm. Below, statistical analysis (n = 4 each); C: Scheme illustrating the Serca2^Villinhomo mice; after Tx-induction exons 2 + 3 of Serca2 are deleted in the adult Villin⁺ lineages (n = 4 each); D: Survival curves of DSerca2^Villinhomo mice (n = 10) compared with corn oil-treated controls (n = 10); E: Serum biochemical analysis of DSerca2^Villinhomo (3 days post-Tx; open circles) or corn oil-treated Serca2^Villin control samples (close circles) (n = 4 each); F: Determination of total fat in feces (% of total weight; n = 4 each, independent animals); G and H: Histological analysis of the esophagus and the esophagus-stomach union of DSerca2^Villinhomo mice (3 days post-Tx) and corn oil-treated controls (n = 3 each; independent animals, several sections were analyzed for each animal). Bar sizes are included. Assays were performed three times and data are expressed as mean ± SD. ^aP < 0.05. ^bP < 0.02. ^cP < 0.002. The online version of the manuscript includes the following information: Electron microscopy analysis of small intestine after conditional deletion of Serca2 in the Bmi1⁺ stem cell compartment (Supplementary Figure 5). ER: Endoplasmic reticulum; Tx: Tamoxifen; SERCA: Sarco(endo)plasmic reticulum calcium ATPases; Lox P: Locus of X-over P1.