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Published on: February 22, 2015
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A Bmp Reporter Transgene Mouse Embryonic Stem Cell Model as a Tool to Identify and Characterize Chemical Teratogens
Josephine Kugler1, Julian Tharmann1, Susana M Chuva de Sousa Lopes2
1*German Federal Institute for Risk Assessment (BfR), Department of Chemicals and Product Safety Berlin, 10589 Berlin, Germany;
Summary
A novel reporter embryonic stem cell (ESC) line effectively identifies chemical teratogens. This tool quantizes dose-dependent toxicity, aiding in the discovery of embryonic developmental risks.
Area of Science:
- Developmental Biology
- Toxicology
- Stem Cell Biology
Background:
- Embryonic stem cells (ESCs) are crucial for studying gene function and modeling genetic diseases.
- In vitro ESC applications include pharmaceutical and toxicological testing, particularly for identifying teratogenic compounds.
- Traditional methods for teratogen identification can be enhanced with new reporter systems.
Purpose of the Study:
- To introduce and validate a novel bone morphogenetic protein (Bmp)-reporter ESC line for identifying chemical teratogens.
- To assess the utility of this reporter system in quantifying the effects of known teratogens.
Main Methods:
- Isolation of a Bmp-reporter ESC line from a transgenic mouse model.
- Utilizing green fluorescent protein (GFP) expression mediated by Bmp signaling to detect teratogenic effects.
- Quantifying dose- and time-dependent responses to valproic acid and retinoic acid.
Main Results:
- The Bmp-reporter ESC line successfully detected dose- and time-dependent effects of valproic acid and retinoic acid.
- Significant toxic effects were observed at concentrations comparable to classical embryonic stem cell tests.
- Reporter gene expression occurred in diverse cell types, including endothelial and endodermal cells.
Conclusions:
- The Bmp-reporter ESC line is a valuable new tool for identifying and characterizing chemical teratogens.
- This system aids in understanding the mechanisms of embryonic toxicity.
- The reporter system demonstrates sensitivity and broad applicability in toxicological screening.
