| First Author | Cho HY | Year | 2002 |
| Journal | Am J Respir Cell Mol Biol | Volume | 26 |
| Issue | 1 | Pages | 42-51 |
| PubMed ID | 11751202 | Mgi Jnum | J:73581 |
| Mgi Id | MGI:2155920 | Doi | 10.1165/ajrcmb.26.1.4536 |
| Citation | Cho HY, et al. (2002) Linkage Analysis of Susceptibility to Hyperoxia. Nrf2 is a candidate gene. Am J Respir Cell Mol Biol 26(1):42-51 |
| abstractText | A strong role for reactive oxygen species (ROS) has been proposed in the pathogenesis of a number of lung diseases. Hyperoxia (> 95% oxygen) generates ROS and extensive lung damage, and has been used as a model of oxidant injury. However, the precise mechanisms of hyperoxia-induced toxicity have not been completely clarified. This study was designed to identify hyperoxia susceptibility genes in C57BL/6J (susceptible) and C3H/HeJ (resistant) mice. The quantitative phenotypes used for this analysis were pulmonary inflammatory cell influx, epithelial cell sloughing, and hyperpermeability. Genome-wide linkage analyses of intercross (F(2)) and recombinant inbred cohorts identified significant and suggestive quantitative trait loci on chromosomes 2 (hyperoxia susceptibility locus 1 [Hsl1]) and 3 (Hsl2), respectively. Comparative mapping of Hsl1 identified a strong candidate gene, Nfe2l2 (nuclear factor, erythroid derived 2, like 2 or Nrf2) that encodes a transcription factor NRF2 which regulates antioxidant and phase 2 gene expression. Strain-specific variation in lung Nrf2 messenger RNA expression and a T --> C substitution in the B6 Nrf2 promoter that cosegregated with susceptibility phenotypes in F(2) animals supported Nrf2 as a candidate gene. Results from this study have important implications for understanding the mechanisms through which oxidants mediate the pathogenesis of lung disease. |
