Premium
Generation of transgenic mice that conditionally express microRNA miR ‐145
Author(s) -
Sawant Dwitiya,
Klevenow Emilie,
Baeten Jeremy T.,
Thomas Shelby,
Manivannan Sathiyanarayanan,
Conway Simon J.,
Lilly Brenda
Publication year - 2020
Publication title -
genesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.093
H-Index - 110
eISSN - 1526-968X
pISSN - 1526-954X
DOI - 10.1002/dvg.23385
Subject(s) - microrna , transgene , biology , genetically modified mouse , cre recombinase , psychological repression , phenotype , microbiology and biotechnology , cancer research , genetics , gene expression , gene
Summary MicroRNAs are modulators of cellular phenotypes and their functions contribute to development, homeostasis, and disease. miR‐145 is a conserved microRNA that has been implicated in regulating an array of phenotypes. These include supporting smooth muscle differentiation, repression of stem cell pluripotency, and inhibition of tumor growth and metastasis. Previously, our lab demonstrated that miR‐145 acts to suppress cardiac fibrosis through inhibition of the TGF‐β signaling pathway. The range of effects that miR‐145 has on different cell types makes it an attractive microRNA for further study. Here we describe the generation of transgenic mice that conditionally express miR‐145 through Cre recombinase‐mediated activation. Characterization of individual founder lines indicates that overexpression of miR‐145 in the developing cardiovascular system has detrimental effects, with three independent miR‐145 transgenic lines exhibiting Cre‐dependent lethality. Expression analysis demonstrates that the transgene is robustly expressed and our analysis reveals a novel downstream target of miR‐145 , Tnnt2 . The miR‐145 transgenic mice represent a valuable tool to understand the role of miR‐145 in diverse cell types and to address its potential as a therapeutic mediator for the treatment of disease.