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Publication : Global microRNA expression is essential for murine mast cell development in vivo.

First Author  Oh SY Year  2014
Journal  Exp Hematol Volume  42
Issue  10 Pages  919-23.e1
PubMed ID  25201754 Mgi Jnum  J:230197
Mgi Id  MGI:5755747 Doi  10.1016/j.exphem.2014.07.266
Citation  Oh SY, et al. (2014) Global microRNA expression is essential for murine mast cell development in vivo. Exp Hematol 42(10):919-23.e1
abstractText  MicroRNAs (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 x 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 x Dicer +/+ and heterozygous Mcpt5-Cre x Dicer fl/+ mice show marked hypothermia with antigen; however, homozygous Mcpt5-Cre x 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 vivo.
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