Fig. 4: Tissue-specific overexpression in vivo.

a LNPCre was delivered to R26LSL-SAM/+ to activate SAM expression in the liver (n = 3); data was plotted as the mean per group +/− SD. p-values of each comparison can be found in Supplementary Table 4. Three replicates were conducted with similar results. b A western blot showing dCas9SAM expression (219 kDa) in R26LSL-SAM/+ tissues treated with LNPCre. dCas9SAM signals are normalized to actin (41 kDa). One repeat was completed with similar results. c Expression profile of Tsx in R26LSL-SAM/4aTsx tissues with and without LNPCre treatment. Tsx expression relative to R26SAM/+ was determined by RT-qPCR (n = 3) and plotted as the mean per group +/− SD; p = 0.000082. d RNAscope of hypothalamus sections showing DAPI (blue), Pomc (green) and Ttr (magenta) in R26SAM/+ and WT mice (n = 2). e Zoom of ventromedial hypothalamus showing co-localization of Pomc and Ttr. Green arrows are pointing to white patches that represent co-localization. Additional individual repeats have not been conducted. f Graphical protocol for harvest and culture of the organ of Corti. g RT-qPCR determination of Ttr (p = 0.0015), Ldlr (p = 0.001395), and Pcsk9 (p = 0.000052) expression levels in organ of Corti explant cultures to R26SAM/SAM. Results are plotted as the mean per group +/− SD (n = 3). Asterisks (*) indicates significance, and the number of asterisks indicates the number of 0s after the decimal point. One-tailed, unpaired Student’s t-test for (a, c, g).