title: Global microRNA expression is essential for murine mast cell development in vivo.
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.
authors.affiliation: Division of Allergy and Clinical Immunology, Johns Hopkins Allergy and Asthma Center, Baltimore, MD, USA.
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Oh
authors.affiliation: Division of Pediatric Hematology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Brandal
authors.affiliation: Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Cancer Research Institute, Indianapolis, IN, USA.
authors.forename: Reuben
authors.initials: R
authors.lastname: Kapur
authors.affiliation: Division of Allergy and Clinical Immunology, Johns Hopkins Allergy and Asthma Center, Baltimore, MD, USA; Section of Allergy and Clinical Immunology, Yale School of Medicine, New Haven, CT, USA.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Division of Pediatric Hematology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: ctakemot@jhmi.edu.
authors.forename: Clifford M
authors.initials: CM
authors.lastname: Takemoto
mesh_terms: D000707:Anaphylaxis / Q000276:immunology; D000818:Animals; D002452:Cell Count; D003433:Crosses, Genetic; D053487:DEAD-box RNA Helicases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation; D005838:Genotype; D006801:Humans; D007035:Hypothermia / Q000276:immunology; D007114:Immunization; D008407:Mast Cells / Q000166:cytology* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics*; D009928:Organ Specificity; D010047:Ovalbumin / Q000276:immunology / Q000633:toxicity; D010537:Peritoneum / Q000276:immunology / Q000473:pathology; D043244:Ribonuclease III / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D012709:Serum Albumin / Q000276:immunology; D012867:Skin / Q000276:immunology / Q000473:pathology; D013270:Stomach / Q000276:immunology / Q000473:pathology
chemical_list: D035683:MicroRNAs; D012709:Serum Albumin; D010047:Ovalbumin; C509781:Dicer1 protein, mouse; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases