RNA-seq profiling of neural tissue from mouse embryos with combined loss of p53 and Bim

Neural tube defects (NTDs) are common birth defects in humans and show an unexplained female bias. Female mice lacking the tumor suppressor p53 display NTDs with incomplete penetrance. We found that the combined loss of pro-apoptotic BIM and p53 caused 100% penetrant, female-exclusive NTDs, which allowed us to investigate the female-specific functions of p53. We report that female p53–/– neural tube samples show fewer cells with inactive X markers Xist and H3K27me3, and a concomitant increase in biallelic expression of the X-linked genes, Huwe1 and Usp9x. The depletion of Xist and increase X-linked gene expression was confirmed by RNA sequencing. Compound mutant mice were generated by inter-crossing single mutant strains previously described (PMID: 7922305, PMID: 10576740). RNA was extracted from neural tissue from E9.5 Bim-/+ mouse embryos. RNA-seq profiling was undertaken for n=4 affected female embryos (p53 knockout), n=4 control male mice (p53 knockout) and n=3 control female embryos (p53 wildtype).