Embryonic Lethality and Fetal Liver Apoptosis in Mice Lacking the C-raf-1 Gene

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2001 Apr 11

PMID 11296228

Citations 107

Authors

M Mikula

M Schreiber

Z Husak

L Kucerova

J Ruth

R Wieser

K Zatloukal

H Beug

E F Wagner

M Baccarini

Affiliations

Soon will be listed here.

Abstract

The Raf kinases play a key role in relaying signals elicited by mitogens or oncogenes. Here, we report that c-raf-1(-/-) embryos are growth retarded and die at midgestation with anomalies in the placenta and in the fetal liver. Although hepatoblast proliferation does not appear to be impaired, c-raf-1(-/-) fetal livers are hypocellular and contain numerous apoptotic cells. Similarly, the poor proliferation of Raf-1(-/-) fibroblasts and hematopoietic cells cultivated in vitro is due to an increase in the apoptotic index of these cultures rather than to a cell cycle defect. Furthermore, Raf-1- deficient fibroblasts are more sensitive than wild- type cells to specific apoptotic stimuli, such as actinomycin D or Fas activation, but not to tumor necrosis factor-alpha. MEK/ERK activation is normal in Raf-1-deficient cells and embryos, and is probably mediated by B-RAF. These results indicate that the essential function of Raf-1 is to counteract apoptosis rather than to promote proliferation, and that effectors distinct from the MEK/ERK cascade must mediate the anti-apoptotic function of Raf-1.

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