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Home   •   Spotlight  •  medsci04  •   Most Cited Journal Articles 2004-Medical Sciences (7)

Most Cited Journal Articles 2004-Medical Sciences

Following is a CAS database record representing a highly cited journal article.

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CAS indexed 2 chemical substances from this document. CAS subject entries for this document include: Mouse (Mus musculus); Receptors; Gene, animal; and 8 additional concepts.

CAPLUS COPYRIGHT 2005 ACS on STN

TITLE:	Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene
AUTHOR(S):	Poltorak, Alexander; He, Xiaolong; Smirnova, Irina; Liu, Mu-Ya; Van Huffel, Christophe; Du, Xin; Birdwell, Dale; Alejos, Erica; Silva, Maria; Galanos, Chris; Freudenberg, Marina; Ricciardi-Castagnoli, Paola; Layton, Betsy; Beutler, Bruce
CORPORATE SOURCE:	Howard Hughes Med. Inst. and the Dep. of Internal Medicine, Univ. Texas Southwestern Med. Cent., Dallas, TX, 75235-9050, USA
SOURCE:	Science (Washington, D. C.) (1998), 282(5396), 2085-2088 CODEN: SCIEAS; ISSN: 0036-8075
PUBLISHER:	American Association for the Advancement of Science
LANGUAGE:	English

ABSTRACT:
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-neg. 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-neg. sepsis, leaving most aspects of immune function intact.