Oh, Sun YoungBrandal, StephanieKapur, ReubenZhu, ZhouTakemoto, Clifford2016-08-192016-08-192014-10Oh, S. Y., Brandal, S., Kapur, R., Zhu, Z., & Takemoto, C. M. (2014). Global microRNA expression is essential for murine mast cell development in vivo. Experimental Hematology, 42(10), 919–923.e1. http://doi.org/10.1016/j.exphem.2014.07.266https://hdl.handle.net/1805/10740MicroRNAs (miRNAs) are small, noncoding RNAs that have been shown to play a critical role in normal physiology and disease, such as hematopoietic development and cancer. However, their role in mast-cell function and development is poorly understood. The major objective of this study was to determine how global miRNA expression affects mast-cell physiology. The RNase III endonuclease, Dicer, is required for the processing of pre-miRNAs into mature miRNAs. To investigate the effect 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 connective tissue mast cells were crossed with mice carrying the floxed conditional Dicer allele (Dicer fl/fl). Mcpt5-Cre × Dicer fl/fl mice with homozygous Dicer gene deletion in mast cells 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 immunoglobulin-E-dependent passive systemic anaphylaxis murine model. Immunoglobulin-E-sensitized wild type Mcpt5-Cre × Dicer +/+ and heterozygous Mcpt5-Cre × Dicer fl/+ mice show marked hypothermia with antigen; however, homozygous Mcpt5-Cre × Dicer fl/fl mice were completely unresponsive to antigen challenge. These studies suggest a critical role for Dicer and miRNA expression for establishment of tissue compartments of functional mast cells in vivoen-USPublisher PolicyDEAD-box RNA HelicasesMast CellsOvalbuminPeritoneumRibonuclease IIISkinStomachArticle