Endotoxin-tolerant Mice Have Mutations in Toll-like Receptor 4 (Tlr4)

Autor: Sophie Clermont, Danielle Malo, Gary Leveque, Line Larivière, Salman T. Qureshi, Karen J. Moore, Philippe Gros
Rok vydání: 1999
Předmět:
Lipopolysaccharides
DNA Mutational Analysis
Molecular Sequence Data
Immunology
Mutant
Mutation
Missense
Mice
Inbred Strains
Receptors
Cell Surface
Locus (genetics)
Biology
Mice
Species Specificity
Inbred strain
Commentaries
Animals
Drosophila Proteins
Humans
Point Mutation
Immunology and Allergy
Amino Acid Sequence
Cloning
Molecular
Allele
Gene
Expressed Sequence Tags
Genetics
Mice
Inbred C3H
Toll-like receptor
Membrane Glycoproteins
Sequence Homology
Amino Acid
Reverse Transcriptase Polymerase Chain Reaction
Point mutation
Homozygote
Toll-Like Receptors
Chromosome Mapping
Molecular biology
Endotoxemia
Mice
Mutant Strains
Endotoxins
Mice
Inbred C57BL
Toll-Like Receptor 4
Amino Acid Substitution
TLR4
lipids (amino acids
peptides
and proteins)
Sequence Alignment
Gene Deletion
Signal Transduction
Zdroj: The Journal of Experimental Medicine
ISSN: 1540-9538
0022-1007
Popis: Bacterial lipopolysaccharide (LPS) provokes a vigorous, generalized proinflammatory state in the infected host. Genetic regulation of this response has been localized to the Lps locus on mouse chromosome 4, through study of the C3H/HeJ and C57BL/10ScCr inbred strains. Both C3H/HeJ and C57BL/10ScCr mice are homozygous for a mutant Lps allele (Lpsd/d) that confers hyporesponsiveness to LPS challenge, and therefore exhibit natural tolerance to its lethal effects. Genetic and physical mapping of 1,345 backcross progeny segregating this mutant phenotype confined Lps to a 0.9-cM interval spanning 1.7 Mb. Three transcription units were identified within the candidate interval, including Toll-like receptor 4 (Tlr4), part of a protein family with members that have been implicated in LPS-induced cell signaling. C3H/HeJ mice have a point mutation within the coding region of the Tlr4 gene, resulting in a nonconservative substitution of a highly conserved proline by histidine at codon 712, whereas C57BL/ 10ScCr mice exhibit a deletion of Tlr4. Identification of distinct mutations involving the same gene at the Lps locus in two different hyporesponsive inbred mouse strains strongly supports the hypothesis that altered Tlr4 function is responsible for endotoxin tolerance.
Databáze: OpenAIRE
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