A locus on chromosome 9 is associated with differential response of 129S1/SvImJ and FVB/NJ strains of mice to systemic LPS.
A locus on chromosome 9 is associated with differential response of 129S1/SvImJ and FVB/NJ strains of mice to systemic LPS.
复制标题
9 号染色体上的一个位点与 129S1/SvImJ 和 FVB/NJ 品系小鼠对全身 LPS 的差异反应相关。
DOI：
10.1007/s00335-011-9340-8
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Schwartz,DavidA
中科院分区：
文献类型：
--
作者：
Yang,IvanaV;Rutledge,HollyR;Yang,Jun;Warg,LauraA;Sevilla,SergioD;Schwartz,DavidA
Although polymorphisms in TLR receptors and downstream signaling molecules affect the innate immune response, these variants account for only a portion of the ability of the host to respond to microorganisms. To identify novel genes that regulate the host response to systemic lipopolysaccharide (LPS), we created an F2 intercross between susceptible (FVB/NJ) and resistant (129S1/SvImJ) strains, challenged F2 progeny with LPS via intraperitoneal injection, and phenotyped 605 animals for survival and another 500 mice for serum concentrations of IL-1β and IL-6. Genome-wide scans were performed on pools of susceptible and resistant mice for survival, IL-1β, and IL-6. This approach identified a locus on the telomeric end of the q arm of chromosome 9 (0–40 Mb) that was associated with the differences in morbidity and serum concentrations of IL-1β and IL-6 following systemic LPS in FVB/NJ and 129S1/SvImJ strains of mice. Fine mapping narrowed the locus to 3.7 Mb containing 11 known genes, among which are three inflammatory caspases. We studied expression of genes within the locus by quantitative RT-PCR and showed thatCasp1andCasp12levels are unaffected by LPS in both strains, whereasCasp4is highly induced by LPS in FVB/NJ but not in 129S1/SvImJ mice. In conclusion, our mapping results indicate that a 3.7-Mb region on chromosome 9 contains a gene that regulates differential response to LPS in 129S1/SvImJ and FVB/NJ strains of mice. Differences in the induction ofCasp4expression by LPS in the two strains suggest thatCasp4is the most likely candidate gene in this region.
