A locus on chromosome 9 is associated with differential response of 129S1/SvImJ and FVB/NJ strains of mice to systemic LPS

被引：0
作者：
Ivana V. Yang
Holly R. Rutledge
Jun Yang
Laura A. Warg
Sergio D. Sevilla
David A. Schwartz
机构：
[1] National Jewish Health,Center for Genes, Environment and Health and Department of Medicine
[2] University of Colorado School of Medicine,Department of Medicine
[3] National Institutes of Health,National Institute of Environmental Health Sciences
[4] Kendle International,Project Management
来源：
Mammalian Genome | 2011年 / 22卷
关键词：
Recombinant Inbred; Inflammasome Activation; Putative Transcription Factor Binding Site; Innate Immune Gene; Serum Cytokine Concentration;
D O I：
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学科分类号：
摘要：
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 that Casp1 and Casp12 levels are unaffected by LPS in both strains, whereas Casp4 is 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 of Casp4 expression by LPS in the two strains suggest that Casp4 is the most likely candidate gene in this region.
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页码：518 / 529
页数：11
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