MCB Accepts, published online ahead of print on 19 October 2009

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Mol. Cell. Biol. doi:10.1128/MCB.01155-09
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Functional co-operation of the pro-apoptotic Bcl2-family proteins Bmf and Bim in vivo

Anette Hübner, Julie Cavanagh-Kyros, Mercedes Rincon, Richard A. Flavell, and Roger J. Davis^*

Howard Hughes Medical Institute and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA; Immunology Program, Department of Medicine, University of Vermont, Burlington, VT 05405, USA; Howard Hughes Medical Institute and Department of Immunobiology, Yale University School of Medicine, Yale University, New Haven, Connecticut 06520, USA

Bcl2-modifying factor (Bmf) is a member of the BH3-only group of pro-apoptotic proteins. To test the role of Bmf in vivo, we constructed mice with a series of mutated Bmf alleles that disrupt Bmf expression, prevent Bmf phosphorylation by the cJun NH₂-terminal kinase (JNK) on Ser ⁷⁴, or mimic Bmf phosphorylation on Ser ⁷⁴. We report that loss of Bmf causes defects in uterovaginal development, including an imperforate vagina and hydrometrocolpos. We also show that phosphorylation of Bmf on Ser ⁷⁴ can contribute to a moderate increase in Bmf activity. Studies of compound mutants with the related gene Bim demonstrated that Bim and Bmf exhibit partially redundant functions in vivo. Thus, developmental ablation of interdigital webbing on mouse paws and normal lymphocyte homeostasis require the co-operative activity of Bim and Bmf.