Extended Data Fig. 4: Correction of Ifnr locus copy number prevents embryonic heart malformations in a mouse model of Down syndrome.
a, Representative images of haematoxylin and eosin stained serial sections through entire murine hearts at embryonic day (E)15.5. Serial sections were cut through the entire region of the developing heart with transverse directionality indicated by arrow. Images represent a total of 58 formalin fixed paraffin embedded embryos that were processed and analyzed across four independent experiment batches; R: right, L: left, A: atrium, V: ventricle. WT (n = 24, 12 male, 12 female), Dp16 (n = 18, 9 male, 7 female, 2 undocumented sex), and Dp162xIfnrs (n = 16, 4 male, 12 female). b, Western blot analysis of total and phosphorylated STAT1 at tyrosine 701 (pSTAT1) protein from developing hearts at E15.5 of wild-type (WT), heterozygous Ifnr knockout mice (WT1xIfnrs), Dp16, and Dp162xIfnrs animals, where n = 3/4/3/3 per group (undocumented sex ratio), respectively. c, Heatmaps displaying Normalized Enrichment Scores (NES) from Gene Set Enrichment Analysis (GSEA) of transcriptome changes in E18.5 and adult heart tissue, sorted by NES for Dp16 versus WT. E18.5 - WT (n = 6, 4 male, 2 female), Dp16 (n = 6, 3 male, 3 female), Dp162xIfnrs (n = 6, 3 male, 3 female), Adult - WT (n = 5, 2 male, 3 female), Dp16 (n = 6, 3 male, 3 female), Dp162xIfnrs (n = 5, 3 male, 2 female); asterisks indicate q < 0.1 defined by GSEA after Benjamini-Hochberg correction. d, Heatmaps displaying median RPKM expression Z-scores per genotype for example genes from gene sets dysregulated in E12.5 and adult heart tissue. e, Sina plots displaying expression levels in adult heart tissue for example genes. q-values determined by DESeq2 with significance set at q < 0.1 after Benjamini-Hochberg correction. In d-e, sample sizes are as described in c.
