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Cutting edge: Toll-like receptor 4 (TLR4)-deficient mice are hyporesponsive to lipopolysaccharide: evidence for TLR4 as the Lps gene product.

The human homologue of Drosophila Toll (hToll), also called Toll-like receptor 4 (TLR4), is a recently cloned receptor of the IL-1/Toll receptor family. Interestingly, the TLR4 gene has been localized to the same region to which the Lps locus (endotoxin unresponsive gene locus) is mapped. To examine the role of TLR4 in LPS responsiveness, we have generated mice lacking TLR4. Macrophages and B cells from TLR4-deficient mice did not respond to LPS. All these manifestations were quite similar to those of LPS-hyporesponsive C3H/HeJ mice. Furthermore, C3H/HeJ mice have, in the cytoplasmic portion of TLR4, a single point mutation of the amino acid that is highly conserved among the IL-1/Toll receptor family. Overexpression of wild-type TLR4 but not the mutant TLR4 from C3H/HeJ mice activated NF-kappaB. Taken together, the present study demonstrates that TLR4 is the gene product that regulates LPS response.

Pubmed ID: 10201887


  • Hoshino K
  • Takeuchi O
  • Kawai T
  • Sanjo H
  • Ogawa T
  • Takeda Y
  • Takeda K
  • Akira S


Journal of immunology (Baltimore, Md. : 1950)

Publication Data

April 1, 1999

Associated Grants


Mesh Terms

  • Amino Acid Sequence
  • Animals
  • B-Lymphocytes
  • Drosophila Proteins
  • Lipopolysaccharides
  • Macrophages, Peritoneal
  • Membrane Glycoproteins
  • Mice
  • Mice, Inbred C3H
  • Mice, Knockout
  • Molecular Sequence Data
  • Point Mutation
  • Receptors, Cell Surface
  • Toll-Like Receptor 4
  • Toll-Like Receptors