Publication Date:
1998-12-16
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Poltorak, A -- He, X -- Smirnova, I -- Liu, M Y -- Van Huffel, C -- Du, X -- Birdwell, D -- Alejos, E -- Silva, M -- Galanos, C -- Freudenberg, M -- Ricciardi-Castagnoli, P -- Layton, B -- Beutler, B -- New York, N.Y. -- Science. 1998 Dec 11;282(5396):2085-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute and the Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75235-9050, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9851930" target="_blank"〉PubMed〈/a〉
Keywords:
Amino Acid Sequence
;
Animals
;
Chromosome Mapping
;
Cloning, Molecular
;
*Drosophila Proteins
;
Genes, Dominant
;
Gram-Negative Bacterial Infections/immunology
;
Homozygote
;
Lipopolysaccharides/*metabolism/pharmacology
;
Macrophages/metabolism
;
Membrane Glycoproteins/chemistry/*genetics/metabolism
;
Mice
;
Mice, Inbred C3H
;
Mice, Inbred C57BL
;
Molecular Sequence Data
;
Mutation, Missense
;
Point Mutation
;
RNA, Messenger/genetics/metabolism
;
Receptors, Cell Surface/chemistry/*genetics/metabolism
;
*Signal Transduction
;
Toll-Like Receptor 4
;
Toll-Like Receptors
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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