Early conditional loss of MT1-MMP in an MT2-MMP–deficient background replicates unconditional loss of both genes and LA disruption. (A) Whole mount images of embryos collected at E12.5 with double-deficiency induced before the formation of the LA via TMX-induced Cre-mediated excision from E7.5 to 11.5. (B-E) Corresponding LA structure of embryos in panel A. (B) Normal LA with abundant FVs and MSs juxtaposed. (C) Equivalent LA structure to that shown in panel B except the embryo is heterozygous for the unconditional MT1-MMP allele. (D) LA from Cre+ placenta displaying a LA morphology equivalent to that found in (1−/−; 2−/−) placentas featuring a compact structure and sparse vessels. Note the many dead cells (arrowheads) and the large distance between FVs and MSs. (E) LA from another Cre+ placenta demonstrating multiple dead cells around the FVs (yellow outline). (F) Relative MT1-MMP mRNA level measured by real-time PCR of embryonic tissues shown in panel A after TMX treatment. Note that TMX treatment in Cre− mice does not affect development. Scale bars: (A) 1 mm; (B-E) 50 μm.