Identification of undescribed Relb expression domains in the murine brain by new Relb:cre-katushka reporter mice.

BACKGROUND: Noncanonical NF-κB signaling through activation of the transcription factor RelB acts as key regulator of cell lineage determination and differentiation in various tissues including the immune system. To elucidate temporospatial aspects of Relb expression, we generated a BAC transgenic knock-in mouse expressing the fluorescent protein Katushka and the enzyme Cre recombinase under control of the murine Relb promoter (RelbCre-Kat mice). RESULTS: Co-expression of Katushka and Relb in fibroblast cultures and tissues of transgenic mice revealed highly specific reporter functions of the transgene. Crossing RelbCre-Kat mice with ROSA26R reporter mice that allow for Cre-mediated consecutive ß-galactosidase or YFP synthesis identified various Relb expression domains in perinatal and mature mice. Besides thymus and spleen, highly specific expression patterns were found in different neuronal domains, as well as in other nonimmune organs including skin, skeletal structures and kidney. De novo Relb expression in the mature brain was confirmed in conditional knockout mice with neuro-ectodermal Relb deletion. CONCLUSION: Our results demonstrate the usability of RelbCre-Kat reporter mice for the detection of de novo and temporarily restricted Relb expression including cell and lineage tracing of Relb expressing cells. Relb expression during mouse embryogenesis and at adulthood suggests, beyond immunity, important functions of this transcription factor in neurodevelopment and CNS function.

The Neurobeachin-like 2 Protein Regulates Mast Cell Homeostasis.

The neurobeachin-like 2 protein (Nbeal2) belongs to the family of beige and Chediak-Higashi (BEACH) domain proteins. Loss-of-function mutations in the human NBEAL2 gene or Nbeal2 deficiency in mice cause gray platelet syndrome, a bleeding disorder characterized by macrothrombocytopenia, splenomegaly, and paucity of α-granules in megakaryocytes and platelets. We found that in mast cells, Nbeal2 regulates the activation of the Shp1-STAT5 signaling axis and the composition of the c-Kit/STAT signalosome. Furthermore, Nbeal2 mediates granule formation and restricts the expression of the transcription factors, IRF8, GATA2, and MITF as well as of the cell-cycle inhibitor p27, which are essential for mast cell differentiation, proliferation, and cytokine production. These data demonstrate the relevance of Nbeal2 in mast cells above and beyond granule biosynthesis.