| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Regular Articles |
From the Department of Pathology,*
University of
Washington, Seattle, Washington; and the Department of
Biology,
Shizuoka University, Shizuoka, Japan
Mice deficient in the nuclear factor 
B (NF-B)-transactivating
gene RelA (p65) die at embryonic days
14–15 with massive liver apoptosis. In the adult liver,
activation of the NF-B heterodimer RelA/p50 can cause hepatocyte
proliferation, apoptosis, or the induction of
acute-phase response genes. We examined, during wild-type fetal
liver development, the expression of the Rel family member
proteins, as well as other proteins known to be important for
NF-B activation. We found these proteins and active NF-B
complexes in the developing liver from at least 2 days before the onset
of lethality observed in RelA knockouts. This suggests
that the timing of NF-B activation is not related to the timing of
lethality. We therefore hypothesized that, in the absence of
RelA, embryos were sensitized to tumor necrosis
factor (TNF) receptor 1 (TNFR-1)-mediated apoptosis.
Thus, we generated mice that were deficient in both
RelA and TNFR-1 to determine whether
apoptotic signaling through TNFR-1 was responsible for the lethal
phenotype. RelA/TNFR-1 double knockout mice survived
embryonic development and were born with normal livers without evidence
of increased hepatocyte apoptosis. These animals became runted
shortly after birth and survived an average of 10 days, dying
from acute hepatitis with an extensive hepatic infiltration of immature
neutrophils. We conclude that neither RelA nor
TNFR-1 is required for liver development and that RelA
protects the embryonic liver from TNFR-1-mediated apoptotic signals.
However, the absence of both TNFR-1 signaling and RelA activity
in newborn mice makes these animals susceptible to endogenous hepatic
infection.
This article has been cited by other articles:
 |
|
 |
|
  A. Wullaert, G. van Loo, K. Heyninck, and R. Beyaert Hepatic Tumor Necrosis Factor Signaling and Nuclear Factor-{kappa}B: Effects on Liver Homeostasis and Beyond Endocr. Rev., June 1, 2007; 28(4): 365 - 386. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. J. Quinton, M. R. Jones, B. T. Simms, M. S. Kogan, B. E. Robson, S. J. Skerrett, and J. P. Mizgerd Functions and Regulation of NF-{kappa}B RelA during Pneumococcal Pneumonia J. Immunol., February 1, 2007; 178(3): 1896 - 1903. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. C. Sadler, K. N. Krahn, N. A. Gaur, and C. Ukomadu Liver growth in the embryo and during liver regeneration in zebrafish requires the cell cycle regulator, uhrf1 PNAS, January 30, 2007; 104(5): 1570 - 1575. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Seymour, J. P. Sundberg, and H. HogenEsch Abnormal lymphoid organ development in immunodeficient mutant mice. Vet. Pathol., July 1, 2006; 43(4): 401 - 423. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Nagashima, V. G. Sasseville, D. Wen, A. Bielecki, H. Yang, C. Simpson, E. Grant, M. Hepperle, G. Harriman, B. Jaffee, et al. Rapid TNFR1-dependent lymphocyte depletion in vivo with a selective chemical inhibitor of IKKbeta Blood, June 1, 2006; 107(11): 4266 - 4273. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-L. Cho, J.-W. Kang, Y.-M. Moon, H.-J. Nam, J.-Y. Jhun, S.-B. Heo, H.-T. Jin, S.-Y. Min, J.-H. Ju, K.-S. Park, et al. STAT3 and NF-{kappa}B Signal Pathway Is Required for IL-23-Mediated IL-17 Production in Spontaneous Arthritis Animal Model IL-1 Receptor Antagonist-Deficient Mice J. Immunol., May 1, 2006; 176(9): 5652 - 5661. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Haouzi, S. Baghdiguian, G. Granier, P. Travo, P. Mangeat, and U. Hibner Three-dimensional polarization sensitizes hepatocytes to Fas/CD95 apoptotic signalling J. Cell Sci., June 15, 2005; 118(12): 2763 - 2773. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. S. Pryhuber, H. L. Huyck, J. M. Roper, J. Cornejo, M. A. O'Reilly, R. H. Pierce, and E. N. Tsitsikov Acute Tumor Necrosis Factor-{alpha}-Induced Liver Injury in the Absence of Tumor Necrosis Factor Receptor-Associated Factor 1 Gene Expression Am. J. Pathol., June 1, 2005; 166(6): 1637 - 1645. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Liu, C. Li, Y. Chen, C. Burnett, X. Y. Liu, S. Downs, R. D. Collins, and J. Hawiger Nuclear Import of Proinflammatory Transcription Factors Is Required for Massive Liver Apoptosis Induced by Bacterial Lipopolysaccharide J. Biol. Chem., November 12, 2004; 279(46): 48434 - 48442. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. G. Cavin, M. Venkatraman, V. M. Factor, S. Kaur, I. Schroeder, F. Mercurio, A. A. Beg, S. S. Thorgeirsson, and M. Arsura Regulation of {alpha}-Fetoprotein by Nuclear Factor-{kappa}B Protects Hepatocytes from Tumor Necrosis Factor-{alpha} Cytotoxicity during Fetal Liver Development and Hepatic Oncogenesis Cancer Res., October 1, 2004; 64(19): 7030 - 7038. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Gugasyan, A. Voss, G. Varigos, T. Thomas, R. J. Grumont, P. Kaur, G. Grigoriadis, and S. Gerondakis The Transcription Factors c-rel and RelA Control Epidermal Development and Homeostasis in Embryonic and Adult Skin via Distinct Mechanisms Mol. Cell. Biol., July 1, 2004; 24(13): 5733 - 5745. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S Finotto, J Siebler, M Hausding, M Schipp, S Wirtz, S Klein, M Protschka, A Doganci, H A Lehr, C Trautwein, et al. Severe hepatic injury in interleukin 18 (IL-18) transgenic mice: a key role for IL-18 in regulating hepatocyte apoptosis in vivo Gut, March 1, 2004; 53(3): 392 - 400. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Y. Zhang, C. L. Green, S. Tao, and P. A. Khavari NF-{kappa}B RelA opposes epidermal proliferation driven by TNFR1 and JNK Genes & Dev., January 1, 2004; 18(1): 17 - 22. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. Zeiss The Apoptosis-Necrosis Continuum: Insights from Genetically Altered Mice Vet. Pathol., September 1, 2003; 40(5): 481 - 495. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Chen, M. Kwong, R. Lu, D. Ginzinger, C. Lee, L. Leung, and J. Y. Chan Nrf1 Is Critical for Redox Balance and Survival of Liver Cells during Development Mol. Cell. Biol., July 1, 2003; 23(13): 4673 - 4686. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Cusson, S. Oikemus, E. D. Kilpatrick, L. Cunningham, and M. Kelliher The Death Domain Kinase RIP Protects Thymocytes from Tumor Necrosis Factor Receptor Type 2-induced Cell Death J. Exp. Med., July 1, 2002; 196(1): 15 - 26. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Chi, F. Diaz-Griffero, C. Wang, J. A. T. Young, and J. Brojatsch An NF-{kappa}B-Dependent Survival Pathway Protects against Cell Death Induced by TVB Receptors for Avian Leukosis Viruses J. Virol., May 3, 2002; 76(11): 5581 - 5587. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. G. Kupfner, J. J. Arcaroli, H.-K. Yum, S. G. Nadler, K.-Y. Yang, and E. Abraham Role of NF-{kappa}B in Endotoxemia-Induced Alterations of Lung Neutrophil Apoptosis J. Immunol., December 15, 2001; 167(12): 7044 - 7051. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Hayashi and D. L. Faustman Genome and Hormones: Gender Differences in Physiology: Selected Contribution: Association of gender-related LMP2 inactivation with autoimmune pathogenesis J Appl Physiol, December 1, 2001; 91(6): 2804 - 2815. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Silverman and T. Maniatis NF-{kappa}B signaling pathways in mammalian and insect innate immunity Genes & Dev., September 15, 2001; 15(18): 2321 - 2342. [Full Text] [PDF]
|
|
|
|
|
|
F. Chen, V. Castranova, and X. Shi New Insights into the Role of Nuclear Factor-{kappa}B in Cell Growth Regulation Am. J. Pathol., August 1, 2001; 159(2): 387 - 397. [Abstract] [Full Text]
|
|
|
|
|
|
E. Alcamo, J. P. Mizgerd, B. H. Horwitz, R. Bronson, A. A. Beg, M. Scott, C. M. Doerschuk, R. O. Hynes, and D. Baltimore Targeted Mutation of TNF Receptor I Rescues the RelA-Deficient Mouse and Reveals a Critical Role for NF-{kappa}B in Leukocyte Recruitment J. Immunol., August 1, 2001; 167(3): 1592 - 1600. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. H. Pierce, J. S. Campbell, A. B. Stephenson, C. C. Franklin, M. Chaisson, M. Poot, T. J. Kavanagh, P. S. Rabinovitch, and N. Fausto Disruption of Redox Homeostasis in Tumor Necrosis Factor-Induced Apoptosis in a Murine Hepatocyte Cell Line Am. J. Pathol., July 1, 2000; 157(1): 221 - 236. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. S. Sylla, K. Murphy, E. Cahir-McFarland, W. S. Lane, G. Mosialos, and E. Kieff The X-linked lymphoproliferative syndrome gene product SH2D1A associates with p62dok (Dok1) and activates NF-kappa B PNAS, June 13, 2000; (2000) 130193097. [Abstract] [Full Text]
|
|
|
|
|
|
B. S. Sylla, K. Murphy, E. Cahir-McFarland, W. S. Lane, G. Mosialos, and E. Kieff The X-linked lymphoproliferative syndrome gene product SH2D1A associates with p62dok (Dok1) and activates NF-kappa B PNAS, June 20, 2000; 97(13): 7470 - 7475. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
