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Vol. 14, No. 1, pp. 23-27, January 1, 2000

RESEARCH COMMUNICATION
Mcl-1 deficiency results in peri-implantation embryonic lethality

Julie L. Rinkenberger,1 Susan Horning,1 Barbara Klocke,1 Kevin Roth,1 and Stanley J. Korsmeyer1,2,3

1 Departments of Medicine and Pathology, Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, Missouri 63110 USA; 2 Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115 USA

We disrupted the Mcl-1 locus in murine ES cells to determine the developmental roles of this Bcl-2 family member. Deletion of Mcl-1 resulted in peri-implantation embryonic lethality. Mcl-1-/- embryos do not implant in utero, but could be recovered at E3.5-4.0. Null blastocysts failed to hatch or attach in vitro, indicating a trophectoderm defect, although the inner cell mass could grow in culture. Of note, Mcl-1-/- blastocysts showed no evidence of increased apoptosis, but exhibited a delay in maturation beyond the precompaction stage. This model indicates that Mcl-1 is essential for preimplantation development and implantation, and suggests that it has a function beyond regulating apoptosis.

[Key Words: Mcl-1; apoptosis; implantation; embryo; blastocyst; Bcl-2 family]


3 Corresponding author.


GENES & DEVELOPMENT 14:23-27 © 2000 by Cold Spring Harbor Laboratory Press  ISSN 0890-9369/00 $5.00

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