Mosaic placental labyrinths containing wild-type trophoblasts and <i>LMα5</i>−/− endothelial cells show LMα5 deposition and normal vascularization.

<p>(A, B) Schematic diagrams of the strategy for conditional mouse <i>LMα5</i> mutation. Using the Cre/loxP system, we generated <i>LMα5^flox/ko</i>; Sox2Cre embryos. Sox2cre, when inherited from a male, is active in epiblast, but not in trophectoderm. Thus, epiblast-derived cells (A), which include the embryo proper as well as extraembryonic endothelial cells, are not able to synthesize LMα5, but trophoblasts, which derive from trophectoderm (B), can. (C–H; C′–H′) Analysis of LMα5 expression and tissue architecture in control (top rows) and <i>LMα5^flox/ko</i>; Sox2cre mutant (bottom rows) embryos. LMα5 was not expressed in the kidney of <i>LMα5^flox/ko</i>; Sox2cre embryos (C′; counterstained with anti-nidogen in D′; compare with control, C and D), which show developmental abnormalities typical of <i>LMα5</i>−/− embryos (E′; arrows indicate exencephaly and syndactyly) not seen in control (E). In contrast, LMα5 was present in the placental labyrinth of <i>LMα5^flox/ko</i>; Sox2cre embryos (F′) and of control (F), and placental LM-111 and PECAM expression and localization were similar to those observed in control <i>LMα5+/</i>− placenta (G–H, G′–H′). Cytokeratin 8 (CK8) was used to identify trophoblasts (G, G′).