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

Exp Hematol. 2014 Oct;42(10):919-23.e1. doi: 10.1016/j.exphem.2014.07.266. Epub 2014 Sep 6.

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 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 vivo.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Anaphylaxis / immunology
  • Animals
  • Cell Count
  • Crosses, Genetic
  • DEAD-box RNA Helicases / deficiency
  • DEAD-box RNA Helicases / genetics
  • DEAD-box RNA Helicases / physiology*
  • Gene Expression Regulation
  • Genotype
  • Humans
  • Hypothermia / immunology
  • Immunization
  • Mast Cells / cytology*
  • Mast Cells / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • MicroRNAs / genetics*
  • Organ Specificity
  • Ovalbumin / immunology
  • Ovalbumin / toxicity
  • Peritoneum / immunology
  • Peritoneum / pathology
  • Ribonuclease III / deficiency
  • Ribonuclease III / genetics
  • Ribonuclease III / physiology*
  • Serum Albumin / immunology
  • Skin / immunology
  • Skin / pathology
  • Stomach / immunology
  • Stomach / pathology

Substances

  • MicroRNAs
  • Serum Albumin
  • Ovalbumin
  • Dicer1 protein, mouse
  • Ribonuclease III
  • DEAD-box RNA Helicases