TP53 and diabetes mellitus: For instance, mice harboring knock-out of the DNA ligase Lig4 (leading to increased endogenous unrepaired DNA strand breaks) and a point mutation in Tp53 (R172P) that mitigates p53-induced apoptosis, leads to very early onset of diabetes, involving both senescent β-cells and progressive loss of β-cell mass due to p53-independent apoptosis (100).