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 Citations (Scopus)

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
Pages (from-to)919-923
Number of pages5
JournalExperimental Hematology
Volume42
Issue number10
DOIs
StatePublished - Oct 1 2014

Fingerprint

MicroRNAs
Mast Cells
Immunoglobulin E
Ribonuclease III
Connective Tissue Cells
Antigens
Small Untranslated RNA
Cell Physiological Phenomena
Endonucleases
Gene Deletion
Anaphylaxis
Hypothermia
Transgenic Mice
Alleles
Skin

ASJC Scopus subject areas

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

Cite this

Global microRNA expression is essential for murine mast cell development invivo. / Oh, Sun Young; Brandal, Stephanie; Kapur, Reuben; Zhu, Zhou; Takemoto, Clifford M.

In: Experimental Hematology, Vol. 42, No. 10, 01.10.2014, p. 919-923.

Research output: Contribution to journalArticle

Oh, Sun Young ; Brandal, Stephanie ; Kapur, Reuben ; Zhu, Zhou ; Takemoto, Clifford M. / Global microRNA expression is essential for murine mast cell development invivo. In: Experimental Hematology. 2014 ; Vol. 42, No. 10. pp. 919-923.
@article{465d06fc0e2245f0879e9e765524a941,
title = "Global microRNA expression is essential for murine mast cell development invivo",
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.",
author = "Oh, {Sun Young} and Stephanie Brandal and Reuben Kapur and Zhou Zhu and Takemoto, {Clifford M.}",
year = "2014",
month = "10",
day = "1",
doi = "10.1016/j.exphem.2014.07.266",
language = "English",
volume = "42",
pages = "919--923",
journal = "Experimental Hematology",
issn = "0301-472X",
publisher = "Elsevier Inc.",
number = "10",

}

TY - JOUR

T1 - Global microRNA expression is essential for murine mast cell development invivo

AU - Oh, Sun Young

AU - Brandal, Stephanie

AU - Kapur, Reuben

AU - Zhu, Zhou

AU - Takemoto, Clifford M.

PY - 2014/10/1

Y1 - 2014/10/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84908365169&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84908365169&partnerID=8YFLogxK

U2 - 10.1016/j.exphem.2014.07.266

DO - 10.1016/j.exphem.2014.07.266

M3 - Article

C2 - 25201754

AN - SCOPUS:84908365169

VL - 42

SP - 919

EP - 923

JO - Experimental Hematology

JF - Experimental Hematology

SN - 0301-472X

IS - 10

ER -