title: Cutting edge: functional characterization of the effect of the C3H/HeJ defect in mice that lack an Lpsn gene: in vivo evidence for a dominant negative mutation.
abstract: A point mutation in the Tlr4 gene, which encodes Toll-like receptor 4, has recently been proposed to underlie LPS hyporesponsiveness in C3H/HeJ mice (Lpsd). The data presented herein demonstrate that F1 progeny from crosses between mice that carry a approximately 9-cM deletion of chromosome 4 (including deletion of LpsTlr4) and C3H/HeJ mice (i.e., Lps0 x Lpsd F1 mice) exhibit a pattern of LPS sensitivity, measured by TNF activity, that is indistinguishable from that exhibited by Lpsn x Lpsd F1 progeny and whose average response is "intermediate" to parental responses. Thus, these data provide clear functional support for the hypothesis that the C3H/HeJ defect exerts a dominant negative effect on LPS sensitivity; however, expression of a normal Toll-like receptor 4 molecule is apparently not required.
authors.affiliation: Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA. vogel@bob.usuf2.usuhs.mil
authors.forename: S N
authors.initials: SN
authors.lastname: Vogel
authors.forename: D
authors.initials: D
authors.lastname: Johnson
authors.forename: P Y
authors.initials: PY
authors.lastname: Perera
authors.forename: A
authors.initials: A
authors.lastname: Medvedev
authors.forename: L
authors.initials: L
authors.lastname: Larivière
authors.forename: S T
authors.initials: ST
authors.lastname: Qureshi
authors.forename: D
authors.initials: D
authors.lastname: Malo
mesh_terms: D000818:Animals; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D029721:Drosophila Proteins; D005838:Genotype; D006239:Haplotypes; D008070:Lipopolysaccharides / Q000276:immunology*; D008264:Macrophages / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D008809:Mice, Inbred C3H / Q000235:genetics* / Q000276:immunology; D020125:Mutation, Missense; D016328:NF-kappa B / Q000378:metabolism; D017354:Point Mutation; D011956:Receptors, Cell Surface / Q000235:genetics*; D017384:Sequence Deletion; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D029721:Drosophila Proteins; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D011956:Receptors, Cell Surface; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha