title: Mcl-1 deficiency results in peri-implantation embryonic lethality.
abstract: 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.
authors.affiliation: Departments of Medicine and Pathology, Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, Missouri 63110 USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Rinkenberger
authors.forename: S
authors.initials: S
authors.lastname: Horning
authors.forename: B
authors.initials: B
authors.lastname: Klocke
authors.forename: K
authors.initials: K
authors.lastname: Roth
authors.forename: S J
authors.initials: SJ
authors.lastname: Korsmeyer
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D003433:Crosses, Genetic; D010064:Embryo Implantation; D005260:Female; D005313:Fetal Death / Q000235:genetics*; D006801:Humans; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D019253:Proto-Oncogene Proteins c-bcl-2
chemical_list: D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2