Comprehensive transcriptome analysis of the neural stem cell and brain in control and NSC-specific (P)RR deficienct mice.

(Pro)renin receptor [(P)RR] is a single-pass transmembrane protein and is widely expressed in mammalian tissues. (P)RR acts as a component of the vacuolar ATPase in lysosomes, contributing to the degradation function and autophagy. Mutations in the (P)RR-coding ATP6AP2 have been reported to cause clinical conditions such as X-linked parkinsonism with spasticity. However, our understanding of the role of (P)RR in the whole brain development remains incomplete. We generated mice with neural stem cell (NSC)-specific (P)RR deficiency (CKO). CKO mice exhibited significant brain atrophy during mid-gestation, leading to perinatal lethality. Fetal CKO brains showed lateral ventricular enlargement with malformation of neocortex and ganglionic eminence (GE) from mid-gestation. CKO brains showed massive apoptosis of neuroblasts and other cell types along with microglial activation at E15. We found that CKO NSCs showed reduced proliferation in the primary neurosphere state, while it was recovered after passage, suggesting that (P)RR is not essential for NSCs self-renewal. We also show that cells in the CKO neocortex showed normal proliferation at E15. In this study, to understand the molecular basis of ATP6AP2-mediated neural stem cell development, we performed a comprehensive analysis of gene expression changes in neural stem cells and whole brain of (P)RR CKO micec using the next-generation RNA sequencing (RNA-seq). Overall design: mRNA profiles of whole brain and neural stem cell were generated by RNA sequencing using the Illumina NexSeq 500 (Illumina).