Department of Lung Development and Remodelling, Max Planck Institute for Heart and Lung Research, member of the German Center for Lung Research (DZL), Bad Nauheim, Germany.
Department of Internal Medicine (Pulmonology), Universities of Giessen and Marburg Lung Center, member of The German Center for Lung Research (DZL), Giessen, Germany.
Pediatr Pulmonol. 2019 Jul;54(7):1060-1077. doi: 10.1002/ppul.24304. Epub 2019 Mar 7.
The laboratory mouse is widely used in preclinical models of bronchopulmonary dysplasia, where lung alveolarization is stunted by exposure of pups to hyperoxia. Whether the diverse genetic backgrounds of different inbred mouse strains impacts lung development in newborn mice exposed to hyperoxia has not been systematically assessed.
Hyperoxia (85% O , 14 days)-induced perturbations to lung alveolarization were assessed by design-based stereology in C57BL/6J, BALB/cJ, FVB/NJ, C3H/HeJ, and DBA/2J inbred mouse strains. The expression of components of the lung antioxidant machinery was assessed by real-time reverse transcriptase polymerase chain reaction and immunoblot.
Hyperoxia-reduced lung alveolar density in all five mouse strains to different degrees (C57BL/6J, 64.8%; FVB/NJ, 47.4%; BALB/cJ, 46.4%; DBA/2J, 45.9%; and C3H/HeJ, 35.9%). Hyperoxia caused a 94.5% increase in mean linear intercept in the C57BL/6J strain, whilst the C3H/HeJ strain was the least affected (31.6% increase). In contrast, hyperoxia caused a 65.4% increase in septal thickness in the FVB/NJ strain, where the C57BL/6J strain was the least affected (30.3% increase). The expression of components of the lung antioxidant machinery in response to hyperoxia was strain dependent, with the C57BL/6J strain exhibiting the most dramatic engagement. Baseline expression levels of components of the lung antioxidant systems were different in the five mouse strains studied, under both normoxic and hyperoxic conditions.
The genetic background of laboratory mouse strains dramatically influenced the response of the developing lung to hyperoxic insult. This might be explained, at least in part, by differences in how antioxidant systems are engaged by different mouse strains after hyperoxia exposure.
实验室小鼠被广泛用于支气管肺发育不良的临床前模型中，在此模型中，通过使幼鼠暴露于高氧环境来抑制肺泡的发育。不同近交系小鼠的遗传背景是否会影响新生小鼠暴露于高氧环境后的肺部发育尚未得到系统评估。
通过基于设计的体视学方法，在 C57BL/6J、BALB/cJ、FVB/NJ、C3H/HeJ 和 DBA/2J 近交系小鼠中评估高氧（85%O2，14 天）诱导的肺泡发育紊乱。通过实时逆转录聚合酶链反应和免疫印迹法评估肺抗氧化机制成分的表达。
高氧降低了所有 5 种小鼠品系的肺泡密度，程度不同（C57BL/6J 为 64.8%；FVB/NJ 为 47.4%；BALB/cJ 为 46.4%；DBA/2J 为 45.9%；C3H/HeJ 为 35.9%）。高氧使 C57BL/6J 品系的平均线性截距增加了 94.5%，而 C3H/HeJ 品系受影响最小（增加 31.6%）。相比之下，高氧使 FVB/NJ 品系的间隔厚度增加了 65.4%，而 C57BL/6J 品系受影响最小（增加 30.3%）。对高氧的反应中肺抗氧化机制成分的表达因品系而异，C57BL/6J 品系表现出最显著的参与。在常氧和高氧条件下，五种研究的小鼠品系的肺抗氧化系统成分的基础表达水平不同。
实验室小鼠品系的遗传背景极大地影响了发育中肺对高氧损伤的反应。这至少可以部分解释为不同小鼠品系在高氧暴露后抗氧化系统的参与方式不同。
