Статья

Defective LPS Signaling in C3H/HeJ and C57BL/10ScCr Mice: Mutations in <i>Tlr4</i> Gene

Alexander PoltorakA. Poltorak, X. He, I. Smirnova, M.-Y. Liu, C. Van Huffel, X. Du, D. Birdwell, E. Alejos, M. Silva, B. Layton, B. Beutler, Howard Hughes Medical Institute and the Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75235–9050 USA. C. Galanos and M. Freudenberg, Max-Planck Institute für Immunobiologie, Freiburg, Germany. P. Ricciardi, CNR–Cellular and Molecular Pharmacology Center, Milan, ItalyXiaolong HeA. Poltorak, X. He, I. Smirnova, M.-Y. Liu, C. Van Huffel, X. Du, D. Birdwell, E. Alejos, M. Silva, B. Layton, B. Beutler, Howard Hughes Medical Institute and the Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75235–9050 USA. C. Galanos and M. Freudenberg, Max-Planck Institute für Immunobiologie, Freiburg, Germany. P. Ricciardi, CNR–Cellular and Molecular Pharmacology Center, Milan, ItalyIrina SmirnovaA. Poltorak, X. He, I. Smirnova, M.-Y. Liu, C. Van Huffel, X. Du, D. Birdwell, E. Alejos, M. Silva, B. Layton, B. Beutler, Howard Hughes Medical Institute and the Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75235–9050 USA. C. Galanos and M. Freudenberg, Max-Planck Institute für Immunobiologie, Freiburg, Germany. P. Ricciardi, CNR–Cellular and Molecular Pharmacology Center, Milan, ItalyMu-Ya LiuA. Poltorak, X. He, I. Smirnova, M.-Y. Liu, C. Van Huffel, X. Du, D. Birdwell, E. Alejos, M. Silva, B. Layton, B. Beutler, Howard Hughes Medical Institute and the Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75235–9050 USA. C. Galanos and M. Freudenberg, Max-Planck Institute für Immunobiologie, Freiburg, Germany. P. Ricciardi, CNR–Cellular and Molecular Pharmacology Center, Milan, ItalyChristophe Van HuffelA. Poltorak, X. He, I. Smirnova, M.-Y. Liu, C. Van Huffel, X. Du, D. Birdwell, E. Alejos, M. Silva, B. Layton, B. Beutler, Howard Hughes Medical Institute and the Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75235–9050 USA. C. Galanos and M. Freudenberg, Max-Planck Institute für Immunobiologie, Freiburg, Germany. P. Ricciardi, CNR–Cellular and Molecular Pharmacology Center, Milan, ItalyXin DuA. Poltorak, X. He, I. Smirnova, M.-Y. Liu, C. Van Huffel, X. Du, D. Birdwell, E. Alejos, M. Silva, B. Layton, B. Beutler, Howard Hughes Medical Institute and the Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75235–9050 USA. C. Galanos and M. Freudenberg, Max-Planck Institute für Immunobiologie, Freiburg, Germany. P. Ricciardi, CNR–Cellular and Molecular Pharmacology Center, Milan, ItalyDale BirdwellA. Poltorak, X. He, I. Smirnova, M.-Y. Liu, C. Van Huffel, X. Du, D. Birdwell, E. Alejos, M. Silva, B. Layton, B. Beutler, Howard Hughes Medical Institute and the Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75235–9050 USA. C. Galanos and M. Freudenberg, Max-Planck Institute für Immunobiologie, Freiburg, Germany. P. Ricciardi, CNR–Cellular and Molecular Pharmacology Center, Milan, ItalyErica AlejosA. Poltorak, X. He, I. Smirnova, M.-Y. Liu, C. Van Huffel, X. Du, D. Birdwell, E. Alejos, M. Silva, B. Layton, B. Beutler, Howard Hughes Medical Institute and the Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75235–9050 USA. C. Galanos and M. Freudenberg, Max-Planck Institute für Immunobiologie, Freiburg, Germany. P. Ricciardi, CNR–Cellular and Molecular Pharmacology Center, Milan, ItalyMaria João SilvaA. Poltorak, X. He, I. Smirnova, M.-Y. Liu, C. Van Huffel, X. Du, D. Birdwell, E. Alejos, M. Silva, B. Layton, B. Beutler, Howard Hughes Medical Institute and the Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75235–9050 USA. C. Galanos and M. Freudenberg, Max-Planck Institute für Immunobiologie, Freiburg, Germany. P. Ricciardi, CNR–Cellular and Molecular Pharmacology Center, Milan, ItalyChris GalanosA. Poltorak, X. He, I. Smirnova, M.-Y. Liu, C. Van Huffel, X. Du, D. Birdwell, E. Alejos, M. Silva, B. Layton, B. Beutler, Howard Hughes Medical Institute and the Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75235–9050 USA. C. Galanos and M. Freudenberg, Max-Planck Institute für Immunobiologie, Freiburg, Germany. P. Ricciardi, CNR–Cellular and Molecular Pharmacology Center, Milan, ItalyMarina A. FreudenbergA. Poltorak, X. He, I. Smirnova, M.-Y. Liu, C. Van Huffel, X. Du, D. Birdwell, E. Alejos, M. Silva, B. Layton, B. Beutler, Howard Hughes Medical Institute and the Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75235–9050 USA. C. Galanos and M. Freudenberg, Max-Planck Institute für Immunobiologie, Freiburg, Germany. P. Ricciardi, CNR–Cellular and Molecular Pharmacology Center, Milan, ItalyPaola Ricciardi‐CastagnoliA. Poltorak, X. He, I. Smirnova, M.-Y. Liu, C. Van Huffel, X. Du, D. Birdwell, E. Alejos, M. Silva, B. Layton, B. Beutler, Howard Hughes Medical Institute and the Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75235–9050 USA. C. Galanos and M. Freudenberg, Max-Planck Institute für Immunobiologie, Freiburg, Germany. P. Ricciardi, CNR–Cellular and Molecular Pharmacology Center, Milan, ItalyBetsy LaytonA. Poltorak, X. He, I. Smirnova, M.-Y. Liu, C. Van Huffel, X. Du, D. Birdwell, E. Alejos, M. Silva, B. Layton, B. Beutler, Howard Hughes Medical Institute and the Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75235–9050 USA. C. Galanos and M. Freudenberg, Max-Planck Institute für Immunobiologie, Freiburg, Germany. P. Ricciardi, CNR–Cellular and Molecular Pharmacology Center, Milan, ItalyBruce BeutlerA. Poltorak, X. He, I. Smirnova, M.-Y. Liu, C. Van Huffel, X. Du, D. Birdwell, E. Alejos, M. Silva, B. Layton, B. Beutler, Howard Hughes Medical Institute and the Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75235–9050 USA. C. Galanos and M. Freudenberg, Max-Planck Institute für Immunobiologie, Freiburg, Germany. P. Ricciardi, CNR–Cellular and Molecular Pharmacology Center, Milan, Italy

1998en

ABI

Аннотация

Mutations of the gene Lps selectively impede lipopolysaccharide (LPS) signal transduction in C3H/HeJ and C57BL/10ScCr mice, rendering them resistant to endotoxin yet highly susceptible to Gram-negative infection. The codominant Lpsd allele of C3H/HeJ mice was shown to correspond to a missense mutation in the third exon of the Toll-like receptor-4 gene (Tlr4), predicted to replace proline with histidine at position 712 of the polypeptide chain. C57BL/10ScCr mice are homozygous for a null mutation of Tlr4. Thus, the mammalian Tlr4 protein has been adapted primarily to subserve the recognition of LPS and presumably transduces the LPS signal across the plasma membrane. Destructive mutations of Tlr4 predispose to the development of Gram-negative sepsis, leaving most aspects of immune function intact.

Перевод пока недоступен

Идентификаторы

DOI: 10.1126/science.282.5396.2085

Цитирования и источники

Цитирований: 3Использованных источников: 0

Показатели — AkademScholar