Age and Sex of Mice Markedly Affect Survival Times Associated with Hyperoxic Acute Lung Injury
| العنوان: | Age and Sex of Mice Markedly Affect Survival Times Associated with Hyperoxic Acute Lung Injury |
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| المؤلفون: | Daniel R. Prows, Jessica J. Smith, Lisa J. Martin, Valentina Pilipenko, William Gibbons |
| المصدر: | PLoS ONE PLoS ONE, Vol 10, Iss 6, p e0130936 (2015) |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Male, Mice, 129 Strain, Genotype, Survival, Acute Lung Injury, Quantitative Trait Loci, Congenic, lcsh:Medicine, Physiology, Lung injury, Quantitative trait locus, Biology, Hyperoxia, Mice, Sex Factors, Inbred strain, Animals, Congenic, Animals, Inbreeding, Allele, lcsh:Science, Genetics, Multidisciplinary, Mortality rate, lcsh:R, Age Factors, Penetrance, Mice, Inbred C57BL, lcsh:Q, Female, Research Article |
| الوصف: | Mortality associated with acute lung injury (ALI) remains substantial, with recent estimates of 35-45% similar to those obtained decades ago. Although evidence for sex-related differences in ALI mortality remains equivocal, death rates differ markedly for age, with more than 3-fold increased mortality in older versus younger patients. Strains of mice also show large differences in ALI mortality. To tease out genetic factors affecting mortality, we established a mouse model of differential hyperoxic ALI (HALI) survival. Separate genetic analyses of backcross and F2 populations generated from sensitive C57BL/6J (B) and resistant 129X1/SvJ (X1) progenitor strains identified two quantitative trait loci (QTLs; Shali1 and Shali2) with strong, equal but opposite, within-strain effects on survival. Congenic lines confirmed these opposing QTL effects, but also retained the low penetrance seen in the 6-12 week X1 control strain. Sorting mice into distinct age groups revealed that 'age at exposure' inversely correlated with survival time and explained reduced penetrance of the resistance trait. While B mice were already sensitive by 6 weeks old, X1 mice maintained significant resistance up to 3-4 weeks longer. Reanalysis of F2 data gave analogous age-related findings, and also supported sex-specific linkage for Shali1 and Shali2. Importantly, we have demonstrated in congenic mice that these age effects on survival correspond with B alleles for Shali1 (6-week old mice more sensitive) and Shali2 (10-week old mice more resistant) placed on the X1 background. Further studies revealed significant sex-specific survival differences in subcongenics for both QTLs. Accounting for age and sex markedly improved penetrance of both QTLs, thereby reducing trait variability, refining Shali1 to |
| تدمد: | 1932-6203 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0d0a722e939692327fb0985b369986b3 https://pubmed.ncbi.nlm.nih.gov/26103466 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....0d0a722e939692327fb0985b369986b3 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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