Mutation of p107 exacerbates the consequences of Rb loss in embryonic tissues and causes cardiac and blood vessel defects
Name
Berman-2009-Mutation of p107 exa.pdf
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1.44 MB
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Author(s)
Lees, Jacqueline
Caron, Alicia M.
Danielian, Paul S.
West, Julie C.
Stone, James R.
Berman, Seth D.
Date Issued
August 2009
Journal
Proceedings of the National Academy of Sciences of the United States of America
Publisher
United States National Academy of Sciences
Citation
Berman, Seth D et al. “Mutation of p107 exacerbates the consequences of Rb loss in embryonic tissues and causes cardiac and blood vessel defects.” Proceedings of the National Academy of Sciences 106.35 (2009): 14932-14936. © 2009 National Academy of Sciences
Version
Final published version
Abstract
The retinoblastoma tumor-suppressor protein, pRb, is a member of the pocket protein family that includes p107 and p130. These proteins have well-defined roles in regulating entry into and exit from the cell cycle and also have cell cycle–independent roles in facilitating differentiation. Here we investigate the overlap between pocket protein's function during embryonic development by using conditional mutant alleles to generate Rb;p107 double-mutant embryos (DKOs) that develop in the absence of placental defects. These DKOs die between e13.5 and e14.5, much earlier than either the conditional Rb or the germline p107 single mutants, which survive to birth or are largely viable, respectively. Analyses of the e13.5 DKOs shows that p107 mutation exacerbates the phenotypes resulting from pRb loss in the central nervous system and lens, but not in the peripheral nervous system. In addition, these embryos exhibit novel phenotypes, including increased proliferation of blood vessel endothelial cells, and heart defects, including double-outlet right ventricle (DORV). The DORV is caused, at least in part, by a defect in blood vessel endothelial cells and/or heart mesenchymal cells. These findings demonstrate novel, overlapping functions for pRb and p107 in numerous murine tissues.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Koch Institute for Integrative Cancer Research at MIT
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
http://dx.doi.org/10.1073/pnas.0902408106
