Integrative Assessment of Chlorine-Induced Acute Lung Injury in Mice

• DOI: 10.1165/rcmb.2012-0026oc
• Publication Date: 2012-03-25T00:14:27Z
• Authors: George D. Leikauf; Hannah Pope-Varsa...; Vincent J. Concel; Pengyuan Liu; Kiflai Bein; Annerose Berndt; Timothy M. Martin; Koustav Ganguly; An Soo Jang; Kelly A. Brant; Richard A. Dopico; Swapna Upadhyay; Y. P. Peter Di; Qian Li; Zhen Hu; Louis J. Vuga; Mario Medvedovic; Naftali Kaminski; Ming You; Danny C. Alexander; Jonathan E. McDunn; Daniel R. Prows; Daren L. Knoell; James P. Fabisiak
• Keywords: Candidate gene; SNP

The genetic basis for the underlying individual susceptibility to chlorine-induced acute lung injury is unknown. To uncover and pathophysiological processes that could provide additional homeostatic capacities during injury, 40 inbred murine strains were exposed chlorine, haplotype association mapping was performed. identified single-nucleotide polymorphism (SNP) associations evaluated through transcriptomic metabolomic profiling. Using ≥ 10% allelic frequency phenotype explained as threshold criteria, promoter SNPs eliminate putative transcriptional factor recognition sites in candidate genes assessed by determining transcript levels microarray reverse real-time PCR chlorine exposure. mean survival time varied approximately 5-fold among strains, SNP 13 on chromosomes 1, 4, 5, 9, 15. Microarrays revealed several differentially enriched pathways, including protein transport (decreased more sensitive C57BLKS/J lung) catabolic process (increased resistant C57BL/10J lung). Lung profiling 95 of 280 metabolites measured altered exposure, included alanine, which decreased than strain, glutamine, increased strain. Genetic from strengthened an integrated assessment using leading associated with mice Klf4, Sema7a, Tns1, Aacs, a gene encodes amino acid carrier, Slc38a4.