Global microRNA expression is essential for mast cell development in vivo (177.18)

Abstract

Abstract microRNAs (miRNAs) are small, non-coding RNAs that have been shown to play a critical role in both normal physiology and disease, such as hematopoietic development and cancer. However, their role in mast cell function and development is unexplored. The RNaseIII endonuclease, Dicer, is required for the processing of pre-miRNAs into mature miRNAs. To investigate the role of global miRNA depletion on mast cells in vivo, we generated a mast cell-specific knock out of Dicer in mice. Transgenic mice (Mcpt5-Cre) that express Cre selectively in mast cells were crossed with mice containing the floxed conditional Dicer allele (Dicer f/f). Mice with both homozygous (Dicer -/-) and heterozygous (Dicer f/-) mast cell-specific deletion of Dicer were viable and healthy. However, Dicer -/- mice were found to have a profound mast cell deficiency with near complete loss of peritoneal, gastrointestinal, and skin mast cells. We examined the in vivo functional consequence of mast cell-specific Dicer deletion using an IgE-dependent passive systemic anaphylaxis (PSA) murine model. IgE sensitized wild type (Dicer f/f) and heterozygous (Dicer f/-) mice show marked hypothermia with antigen; however, homozygous (Dicer -/-) mice were completely unreactive to antigen challenge. These studies suggest a critical role for Dicer and miRNA expression for establishment of mast cell tissue compartments in vivo.