CDB15:0001223 PLAU — LRP1

ABSTRACT: In the article entitled “LDL Receptor-Related Protein Internalizes and Degrades UPA-PAI- Complexes and Is Essential for Embryo Implantation” (Herz et al., Cell 77,41 l421, 1992), we reported the disruption of the mouse gene encoding low density lipoprotein receptor-related protein (LRP). We concluded that LRP is required for embryo implantation based on the following evidence: the absence of homozygous mutant embryos at 9.5 and 10.5 days postcoitum (dpc) in matings of mice heterozygous for the LRP defect, and the expression of LRP in the early postimplantation stage where it is restricted almost exclusively to the trophoblast. In further experiments, we found that 4 of the 34 implanted embryos (Table 1, line 4 in Herz et al., Cell 77, 41 l-421,1992) had been misidentified. These 4 embryos, which were in fact homozygotes, were erroneously classified as heterozygotes. After examining 62 more embryos at 9.5, 10.5, and 13.5 dpc (see Table l), it is now, clear that LRP-deficient blastocysts can implant into the uterus. A delay or arrest in development was apparent in some but not all homozygous early postimplantation embryos that were examined at 9.5 and 10.5 dpc. Of these 11 homozygous embryos, 5 were macroscopically normal in appearance. At 13.5 dpc, all 10 homozygous embryos had arrested at various stages of development, and all 10 were in the process of resorption. Internal hemorrhaging was noted in one 10.5 dpc and in three 13.5 dpc homozygous embryos. We conclude that LRP is required for mouse embryonic development before 13.5 dpc. However, LRP is clearly not essential for embryo implantation as originally reported. We regret this error.