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CUTTING EDGE |
,§
*
Uniformed Services University of the Health Sciences, Bethesda, MD 20814;
Oak Ridge National Laboratories, Oak Ridge, TN 37831; and
Department of Medicine and
§
Department of Human Genetics, McGill University, Montreal, Canada
A point mutation in the Tlr4 gene, which encodes
Toll-like receptor 4, has recently been proposed to underlie LPS
hyporesponsiveness in C3H/HeJ mice (Lpsd).
The data presented herein demonstrate that F1 progeny from
crosses between mice that carry a 
9-cM deletion of chromosome 4
(including deletion of LpsTlr4) and C3H/HeJ
mice (i.e., Lps0 x
Lpsd F1 mice) exhibit a pattern
of LPS sensitivity, measured by TNF activity, that is indistinguishable
from that exhibited by Lpsn x
Lpsd F1 progeny and whose
average response is "intermediate" to parental responses. Thus,
these data provide clear functional support for the hypothesis that the
C3H/HeJ defect exerts a dominant negative effect on LPS sensitivity;
however, expression of a normal Toll-like receptor 4 molecule is
apparently not required.
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E. Faure, O. Equils, P. A. Sieling, L. Thomas, F. X. Zhang, C. J. Kirschning, N. Polentarutti, M. Muzio, and M. Arditi Bacterial Lipopolysaccharide Activates NF-kappa B through Toll-like Receptor 4 (TLR-4) in Cultured Human Dermal Endothelial Cells. DIFFERENTIAL EXPRESSION OF TLR-4 AND TLR-2 IN ENDOTHELIAL CELLS J. Biol. Chem., April 6, 2000; 275(15): 11058 - 11063. [Abstract] [Full Text] [PDF]
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V. C. Dreisbach, S. Cowley, and K. L. Elkins Purified Lipopolysaccharide from Francisella tularensis Live Vaccine Strain (LVS) Induces Protective Immunity against LVS Infection That Requires B Cells and Gamma Interferon Infect. Immun., April 1, 2000; 68(4): 1988 - 1996. [Abstract] [Full Text] [PDF]
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A. M. Soler-Rodriguez, H. Zhang, H. S. Lichenstein, N. Qureshi, D. W. Niesel, S. E. Crowe, J. W. Peterson, and G. R. Klimpel Neutrophil Activation by Bacterial Lipoprotein Versus Lipopolysaccharide: Differential Requirements for Serum and CD14 J. Immunol., March 1, 2000; 164(5): 2674 - 2683. [Abstract] [Full Text] [PDF]
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A. Poltorak, I. Smirnova, R. Clisch, and B. Beutler Limits of a deletion spanning Tlr4 in C57BL/10ScCr mice Innate Immunity, February 1, 2000; 6(1): 51 - 56. [Abstract] [PDF]
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A. D. Wright and S. K. Chapes LPS sensitivity in recombinant mice lacking functional alleles at MHCII, Lps and Nramp1 genes Innate Immunity, October 1, 1999; 5(5-6): 297 - 305. [Abstract] [PDF]
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S. H. Rhee and D. Hwang Murine TOLL-like Receptor 4 Confers Lipopolysaccharide Responsiveness as Determined by Activation of NFkappa B and Expression of the Inducible Cyclooxygenase J. Biol. Chem., October 27, 2000; 275(44): 34035 - 34040. [Abstract] [Full Text] [PDF]
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P. M. C. Wong, Q. Yuan, H. Chen, B. M. Sultzer, and S.-W. Chung A Single Point Mutation at the 3'-Untranslated Region of Ran mRNA Leads to Profound Changes in Lipopolysaccharide Endotoxin-mediated Responses J. Biol. Chem., August 24, 2001; 276(35): 33129 - 33138. [Abstract] [Full Text] [PDF]
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