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

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-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.

Keywords

TLR4Missense mutationLipopolysaccharideBiologyNull alleleGeneExonMutationSignal transductionImmune systemAlleleReceptorMolecular biologyGeneticsImmunology

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Publication Info

Year: 1998
Type: article
Volume: 282
Issue: 5396
Pages: 2085-2088
Citations: 7517
Access: Closed

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APA Style

                            
                                
                                    Alexander Poltorak, 
                                
                                    Xiaolong He, 
                                
                                    Irina Smirnova
                                
                                et al.
                            
                            (1998). 
                            Defective LPS Signaling in C3H/HeJ and C57BL/10ScCr Mice: Mutations in <i>Tlr4</i> Gene. 
                            Science
                            , 282
                            (5396)
                            , 2085-2088.
                            https://doi.org/10.1126/science.282.5396.2085
                        

Identifiers

DOI: 10.1126/science.282.5396.2085