Cutting edge: Functional characterization of the effect of the C3H/HeJ defect in mice that lack an Lps(n) gene: In vivo evidence for a dominant negative mutation
Sn. Vogel et al., Cutting edge: Functional characterization of the effect of the C3H/HeJ defect in mice that lack an Lps(n) gene: In vivo evidence for a dominant negative mutation, J IMMUNOL, 162(10), 1999, pp. 5666-5670
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 (
Lps(d)), The data presented herein demonstrate that F-1 progeny from crosse
s between mice that carry a similar to 9-cM deletion of chromosome 4 (inclu
ding deletion of Lps(Tlr4)) and C3H/HeJ mice (i.e., Lps(0) x Lps(d) F-1 mic
e) exhibit a pattern of LPS sensitivity, measured by TNF activity, that is
indistinguishable from that exhibited by Lps(n) x Lps(d) F-1 progeny and wh
ose average response is "intermediate" to parental responses. Thus, these d
ata provide clear functional support for the hypothesis that the C3H/HeJ de
fect exerts a dominant negative effect on LPS sensitivity; however, express
ion of a normal Toll-like receptor 4 molecule is apparently not required.