LPS-hyporesponsiveness of mnd mice is associated with a mutation in Toll-like receptor 4.
Toll-like receptors (Tlrs) are transmembrane proteins that have recently been shown to play a critical role in the innate immune recognition of microbial constituents. Among this family, Tlr4 is a crucial signal transducer for lipopolysaccharide (LPS), the major component of the Gram-negative bacteria outer cell membrane. In this paper, we report that C57BL/6.KB2-mnd mice, a model of neuronal ceroid lipofuscinosis, do not respond to LPS. This defect is associated with a spontaneous mutation in Tlr4 consisting of a large insertion within exon 2 predicting a frameshift mutation and a truncated protein.
Bihl
F
F
Department of Human Genetics, Centre for the Study of Host Resistance, Montreal General Hospital, Québec, Canada.
Larivière
L
L
Qureshi
S T
ST
Flaherty
L
L
Malo
D
D
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D029721:Drosophila Proteins; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009154:Mutation; D009472:Neuronal Ceroid-Lipofuscinoses / Q000235:genetics; D010641:Phenotype; D011956:Receptors, Cell Surface / Q000235:genetics*; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
D017931:DNA Primers; D029721:Drosophila Proteins; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors