A specific, nonproliferative role for E2F-5 in choroid plexus function revealed by gene targeting
- Geoffrey J. Lindeman,
- Lina Dagnino,
- Stefan Gaubatz,
- Yuhui Xu,
- Roderick T. Bronson,
- Henry B. Warren, and
- David M. Livingston
- The Dana-Farber Cancer Institute/Harvard Medical School, Boston, Massachusetts 02115 USA; Ottawa General Hospital Research Institute, Ottawa, Ontario K1H 8L6 Canada; Tufts University School of Veterinary Medicine, Boston, Massachusetts 02111 USA; Center for Animal Resources and Comparative Medicine/Harvard Medical School, Boston, Massachusetts 02115 USA
Abstract
Homozygous E2F-5 knockout embryos and mice have been generated. Although embryonic development appeared normal, newborn mice developed nonobstructive hydrocephalus, suggesting excessive cerebrospinal fluid (CSF) production. Although the CSF-producing choroid plexus displayed normal cellular organization, it contained abundant electron-lucent epithelial cells, consistent with excessive CSF secretory activity. Moreover, E2F-5 CNS expression in normal animals was largely confined to the choroid plexus. Cell cycle kinetics were not perturbed in homozygous knockout embryo fibroblasts. Thus, E2F-5 is not essential for cell proliferation. Rather, it affects the secretory behavior of a differentiated neural tissue.
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Footnotes
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↵Present address: The Walter and Eliza Hall Institute of Medical Research/Royal Melbourne Hospital, Melbourne, VIC 3050 Australia.
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↵Corresponding author.
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E-MAIL david_livingston{at}dfci.harvard.edu; FAX (617) 632-4381.
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- Received January 20, 1998.
- Accepted February 20, 1998.
- Cold Spring Harbor Laboratory Press
