RNA-seq experiment to investigate the effect of inactivating the Apoptosis Antagonizing Transcription Factor (Aatf)

Human nephronophthisis and related ciliopathies suggest a link between ciliary signaling defects and altered DNA damage responses. The goal of our study is to elucidate the molecular link of both signaling systems as well as the role of altered DNA damage responses in kidney degeneration and fibrosis. The kinase-regulated DNA damage response target Apoptosis Antagonizing Transcription Factor (Aatf) is a master regulator of the p53 response. Upon genetic deletion of Aatf in renal tubular cells we induce progressive renal failure and a phenotype closely resembling human nephronophthisis in mice and are able to show Aatf as a regulator of primary cilia and modulator of the DNA damage response connecting two pathogenetic concepts of nephronophthisi and nephronophthisi-related ciliopathies. The analysis of the RNA-sequencing of four Aatf-knockout mice and four wildtype mice supports the experimental findings.