TY - JOUR
T1 - Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice
T2 - Mutations in Tlr4 gene
AU - Poltorak, Alexander
AU - He, Xiaolong
AU - Smirnova, Irina
AU - Liu, Mu Ya
AU - Van Huffel, Christophe
AU - Du, Xin
AU - Birdwell, Dale
AU - Alejos, Erica
AU - Silva, Maria
AU - Galanos, Chris
AU - Freudenberg, Marina
AU - Ricciardi-Castagnoli, Paola
AU - Layton, Betsy
AU - Beutler, Bruce
PY - 1998/12/11
Y1 - 1998/12/11
N2 - 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 Lps(d) 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.
AB - 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 Lps(d) 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.
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U2 - 10.1126/science.282.5396.2085
DO - 10.1126/science.282.5396.2085
M3 - Article
C2 - 9851930
AN - SCOPUS:0032509295
SN - 0036-8075
VL - 282
SP - 2085
EP - 2088
JO - Science
JF - Science
IS - 5396
ER -