Lps2: A new locus required for responses to lipopolysaccharide, revealed by germline mutagenesis and phenotypic screening

Kasper Hoebe, Xin Du, Jason Goode, Navjiwan Mann, Bruce Beutler

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

Abstract

Both forward and reverse genetic techniques have been used to define components of the mammalian lipopolysaccharide (LPS) receptor. TLR4, identified by a forward genetic approach as the product of the classical Lps locus, is the only known transmembrane component of the mammalian LPS receptor. Gene knockout work has also established that LPS signal transduction requires the integrity of CD14, MD-2, and, in part, MyD88, IRAK4, and TRAF-6. However, there is no reason to believe that these are the only proteins that make up the receptor/transducer apparatus. To examine the possibility that other proteins may be involved, we initiated a mutagenesis program, in which germline mutations are induced in mice using N-ethyl-N-nitrosourea (ENU), and macrophages from individual animals are screened for their competence to respond to LPS. We now report the existence of a new locus, Lps2, which is required for TNF production in response to LPS. The Lps2 mutation that we have identified is co-dominant, is similar in phenotypic effect to Lpsd, and does not represent a novel allele of any of the genes that are known to encode the 'core' LPS signaling apparatus. The Lps2 mutation does not preclude signaling initiated by peptidoglycan or unmethylated DNA. Hence, genetic data suggest that there is at least one 'missing' component of the LPS receptor complex that has yet to be found.

Original languageEnglish (US)
Pages (from-to)250-255
Number of pages6
JournalJournal of Endotoxin Research
Volume9
Issue number4
DOIs
StatePublished - 2003

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Molecular Biology
  • Cell Biology
  • Infectious Diseases

Fingerprint Dive into the research topics of 'Lps2: A new locus required for responses to lipopolysaccharide, revealed by germline mutagenesis and phenotypic screening'. Together they form a unique fingerprint.

Cite this