Transgenic Mouse Models Transferred into the Test Tube: New Perspectives for Developmental Toxicity Testing In Vitro ?

Despite our increasing understanding of molecular mechanisms controlling embryogenesis, the identification and characterization of teratogenic substances still heavily relies on animal testing. Embryonic development depends on cell-autonomous and non-autonomous processes including spatiotemporally r...

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Bibliographic Details
Published in:Trends in pharmacological sciences (Regular ed.) 2016-10, Vol.37 (10), p.822-830
Main Authors: Kugler, Josephine, Luch, Andreas, Oelgeschläger, Michael
Format: Article
Language:English
Subjects:
Advanced Basic Science
Animal Testing Alternatives - methods
Animals
Embryonic Development - drug effects
ESC
Female
Genes, Reporter - genetics
Humans
in vitro testing
iPSC
Mice
Mice, Transgenic
Pregnancy
teratogens
Teratogens - toxicity
Toxicity Tests - methods
transgenic mouse models
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Summary:Despite our increasing understanding of molecular mechanisms controlling embryogenesis, the identification and characterization of teratogenic substances still heavily relies on animal testing. Embryonic development depends on cell-autonomous and non-autonomous processes including spatiotemporally regulated extracellular signaling activities. These have been elucidated in transgenic mouse models harboring easily detectable reporter genes under the control of evolutionarily conserved signaling cascades. We propose combining these transgenic mouse models and cells derived thereof with existing alternative toxicological testing strategies. This would enable the plausibility of in vitro data to be verified in light of in vivo data and, ultimately, facilitate regulatory acceptance of in vitro test methods.
ISSN:0165-6147
1873-3735
DOI:10.1016/j.tips.2016.06.009