PMID- 9989976
OWN - NLM
STAT- MEDLINE
DCOM- 19990603
LR  - 20231105
IS  - 0022-1007 (Print)
IS  - 1540-9538 (Electronic)
IS  - 0022-1007 (Linking)
VI  - 189
IP  - 4
DP  - 1999 Feb 15
TI  - Endotoxin-tolerant mice have mutations in Toll-like receptor 4 (Tlr4).
PG  - 615-25
AB  - 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.
FAU - Qureshi, S T
AU  - Qureshi ST
AD  - Department of Medicine, McGill University, Montreal, Quebec, Canada H3G 1A4.
FAU - Lariviere, L
AU  - Lariviere L
FAU - Leveque, G
AU  - Leveque G
FAU - Clermont, S
AU  - Clermont S
FAU - Moore, K J
AU  - Moore KJ
FAU - Gros, P
AU  - Gros P
FAU - Malo, D
AU  - Malo D
LA  - eng
SI  - GENBANK/AF110133
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Exp Med
JT  - The Journal of experimental medicine
JID - 2985109R
RN  - 0 (Drosophila Proteins)
RN  - 0 (Endotoxins)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (TLR4 protein, human)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Toll-Like Receptors)
SB  - IM
EIN - J Exp Med 1999 May 3;189(9):following 1518
CIN - J Exp Med. 1999 Feb 15;189(4):605-9. PMID: 9989974
MH  - Amino Acid Sequence
MH  - *Amino Acid Substitution
MH  - Animals
MH  - Chromosome Mapping
MH  - Cloning, Molecular
MH  - DNA Mutational Analysis
MH  - *Drosophila Proteins
MH  - Endotoxemia/*genetics
MH  - Endotoxins/*toxicity
MH  - Expressed Sequence Tags
MH  - *Gene Deletion
MH  - Homozygote
MH  - Humans
MH  - Lipopolysaccharides/*toxicity
MH  - Membrane Glycoproteins/genetics/*physiology
MH  - Mice
MH  - Mice, Inbred C3H
MH  - Mice, Inbred C57BL
MH  - Mice, Inbred Strains
MH  - Mice, Mutant Strains
MH  - Molecular Sequence Data
MH  - *Mutation, Missense
MH  - Point Mutation
MH  - Receptors, Cell Surface/genetics/*physiology
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Sequence Alignment
MH  - Sequence Homology, Amino Acid
MH  - Signal Transduction
MH  - Species Specificity
MH  - Toll-Like Receptor 4
MH  - Toll-Like Receptors
PMC - PMC2192941
EDAT- 1999/02/17 00:00
MHDA- 1999/02/17 00:01
PMCR- 1999/08/15
CRDT- 1999/02/17 00:00
PHST- 1999/02/17 00:00 [pubmed]
PHST- 1999/02/17 00:01 [medline]
PHST- 1999/02/17 00:00 [entrez]
PHST- 1999/08/15 00:00 [pmc-release]
AID - 10.1084/jem.189.4.615 [doi]
PST - ppublish
SO  - J Exp Med. 1999 Feb 15;189(4):615-25. doi: 10.1084/jem.189.4.615.