For instance, mice with retinoic acid receptor-γ-deficient (RAR-γ) microenvironment transplanted with wild-type (WT) BM rapidly developed MPN.53 Similarly, the inactivation of the Retinoblastoma (Rb) gene, a central regulator of the cell cycle, in both HSCs and BM microenvironment established a myeloproliferative disorder.54 MPN was also developed after transplanting normal HSCs into mice carrying inactivation of Mind bomb 1 (Mib1), the primary regulator of endocytosis of Notch ligands, in BM stromal cells.55 The gene discussed is RB1; the disease is myeloproliferative disorder.