To evaluate the relative contribution of SIRT4 in mammary tumorigenesis, we then crossed SIRT4-/- mice with MMTV-Neu mice, which mimic the human luminal phenotype and develop spontaneous mammary tumors after acquiring either additional mutations or epigenetic modifications 25, 26 Figure 2F and Figure S4A showed the SIRT4 expression in crossed mice. This evidence concerns the gene SIRT4 and breast cancer.