Moreover, using gain- and loss-of-function genetic approaches to investigate the role of p53 in the phenotypes resulting from loss of hepatic Rps6, we find that hepatoblast-specific stabilization of an Mdm2-resistant p53 mutant only partially mimics the liver disease in S6-deficient livers, while the loss of p53 fails to improve disease induced by Rps6 deficiency indicating that p53 is not the sole pathogenic driver in this model. This evidence concerns the gene RPS6 and liver disorder.