Global microRNA expression is essential for murine mast cell development invivo

Sun Young Oh, Stephanie Brandal, Reuben Kapur, Zhou Zhu, Clifford M. Takemoto

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

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 invivo, 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 invivo 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 invivo.

Original languageEnglish (US)
Pages (from-to)919-923.e1
JournalExperimental Hematology
Volume42
Issue number10
DOIs
StatePublished - Oct 1 2014

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ASJC Scopus subject areas

  • Molecular Biology
  • Hematology
  • Genetics
  • Cell Biology
  • Cancer Research

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