title: Transgenic Mouse Models Transferred into the Test Tube: New Perspectives for Developmental Toxicity Testing In Vitro?
abstract: 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.
authors.affiliation: German Federal Institute for Risk Assessment (BfR), Department of Chemical and Product Safety, Max-Dohrn-Strasse 8-10, 10589 Berlin, Germany.
authors.forename: Josephine
authors.initials: J
authors.lastname: Kugler
authors.affiliation: German Federal Institute for Risk Assessment (BfR), Department of Chemical and Product Safety, Max-Dohrn-Strasse 8-10, 10589 Berlin, Germany. Electronic address: andreas.luch@bfr.bund.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Luch
authors.affiliation: German Federal Institute for Risk Assessment (BfR), Department of Experimental Toxicology and ZEBET, Bf3R, Max-Dohrn-Strasse 8-10, 10589 Berlin, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Oelgeschläger
mesh_terms: D000826:Animal Testing Alternatives / Q000379:methods; D000818:Animals; D047108:Embryonic Development / Q000187:drug effects*; D005260:Female; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D011247:Pregnancy; D013723:Teratogens / Q000633:toxicity*; D018675:Toxicity Tests / Q000379:methods*
chemical_list: D013723:Teratogens
keywords: ESC; iPSC; in vitro testing; teratogens; transgenic mouse models