Gene expression analysis of murine wt and Nbeal2 -/- bone marrow derived mast cells (BMMCs) w/o IL-33 treatment

The Neurobeachin-like 2 (Nbeal2) protein is a BEACH (beige and chediak-higashi) family member. Loss of function mutations of the human NBEAL2 gene result in development of the gray platelet syndrome (GPS) a bleeding disorder characterized by macrothrombocytopenia, splenomegaly, and paucity of α-granules in megakaryocytes, platelets, mast cells (MCs), neutrophils and NK cells. We found that Nbeal2 deficiency in MCs leads to an enhanced resistance to growth factor deprivation, dysregulated distribution of c-Kit and of the multidrug resistant protein-1 (ABCB1), as well as to a pro-inflammatory MC-phenotype. These characteristics are caused by a defective protein degradation machinery resulting in accumulation of RSK and ribosomal proteins (RPS). These data demonstrate that Nbeal2 prevents oncogenic transformation by controlling protein homeostasis (proteostasis) in MCs. 16 samples in four groups: Nbeal2 -/- w/o IL-33: 4 samples; Nbeal2 -/- with IL-33: 4 samples; wildtype w/o IL-33: 4 samples; wildtype with IL-33: 4 samples.