title: Rescue of keratin 18/19 doubly deficient mice using aggregation with tetraploid embryos.
abstract: We have previously shown that the targeted deletions of both type I keratins (K) 18 and 19 cause lethality by embryonic day (e) 9.5 due to fragility and cytolysis of trophoblast giant cells. The development of the embryo proper appeared to be unaffected and its death was caused by nutrient deficiency. In order to address the function of keratins within the embryo proper, lethality due to extraembryonic tissue failure must be overcome. One approach to rescue doubly deficient embryos is by aggregating knockout embryos with tetraploid wild-type embryos. As a general tool, tetraploid aggregation can be used to rescue embryonic lethality caused by defects in extraembryonic tissues like the placenta, trophoblast or yolk sac. We rescued K18-/- K19-/- embryos until e11.5, using this approach, proving that the loss of the keratin cytoskeleton causes defects in the trophoblast giant cell layer, but has no effect on early development of the embryo proper.
authors.affiliation: Institut für Physiologische Chemie, Abteilung für Zellbiochemie, Bonner Forum Biomedizin and LIMES, Universitätsklinikum Bonn, Nussallee 11, D-53115 Bonn, Germany. mhesse@ucalgary.ca
authors.forename: Michael
authors.initials: M
authors.lastname: Hesse
authors.forename: Erica D
authors.initials: ED
authors.lastname: Watson
authors.forename: Tanja
authors.initials: T
authors.lastname: Schwaluk
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Magin
mesh_terms: D000818:Animals; D002678:Chimera; D005455:Fluorescent Antibody Technique; D007633:Keratins / Q000235:genetics* / Q000378:metabolism; D051379:Mice / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D018345:Mice, Knockout; D009030:Mosaicism; D011123:Polyploidy
chemical_list: D007633:Keratins