A distinctive feature of the spontaneous T-ALL model is the frequency of 5′ truncating mutations in the murine Notch1 locus, resulting in translation initiation from a conserved methionine residue within the transmembrane domain and constitutive expression of N1-ICD (Ashworth et al., 2010); such mutations occur only very rarely in humans (Weng et al., 2004). Here, NOTCH1 is linked to acute lymphoblastic leukemia.