Differential lung mechanics are genetically determined in inbred murine strains
Differential lung mechanics are genetically determined in inbred murine strains
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DOI：
10.1152/jappl.1999.86.6.1764
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发表时间：
1999-06-01
影响因子：
3.3
通讯作者：
Mitzner, W
中科院分区：
文献类型：
--
作者：
Tankersley, CG;Rabold, R;Mitzner, W
近交系小鼠品系之间的差异表型已证明肺结构和功能的遗传决定因素。例如，之前的研究报告了标准近交小鼠品系以及 C3H/HeJ (C3) 和 C57BL/6J (B6) 祖代的分离和非分离后代的基线通气测量的表型变异。本研究的目的之一是检验以下假设：差异基线呼吸模式的遗传基础是由于肺机械特性的变化造成的。对标准和重组近交系进行准静态压力-容积曲线，以探索肺力学在确定功能基线通气结果中的相互作用。在气道压力介于 0 和 30 cmH(2)O 之间时，C3 小鼠的肺容量相对于 B6 和 A/J 品系显着更大（P < 0.01）。此外，B6C3F(1)/J 后代表现出与 C3 祖细胞显着不同 (P < 0.01) 的肺机械特性，但与 B6 祖细胞无法区分。通过使用源自 C3 和 B6 祖细胞的重组近交菌株，吸气计时与肺容量和顺应性测量之间的共分离分析表明，基线呼吸模式和压力-容量关系中的菌株差异不具有遗传相关性。尽管 C3 和 B6 小鼠之间肺容量和顺应性的应变差异是可遗传的，但这项研究支持基线吸气时间差异（与小鼠 3 号染色体上的假定基因组区域相关的特征）与 C3 和 B6 祖代及其后代之间差异肺力学之间的分离。
Genetic determinants of lung structure and function have been demonstrated by differential phenotypes among inbred mice strains. For example, previous studies have reported phenotypic variation in baseline ventilatory measurements of standard inbred murine strains as well as segregant and nonsegregant offspring of C3H/HeJ (C3) and C57BL/6J (B6) progenitors. One purpose of the present study is to test the hypothesis that a genetic basis for differential baseline breathing pattern is due to variation in lung mechanical properties. Quasi-static pressure-volume curves were performed on standard and recombinant inbred strains to explore the interactive role of lung mechanics in determination of functional baseline ventilatory outcomes. At airway pressures between 0 and 30 cmH(2)O, lung volumes are significantly (P < 0.01) greater in C3 mice relative to the B6 and A/J strains. In addition, the B6C3F(1)/J offspring demonstrate lung mechanical properties significantly (P < 0.01) different from the C3 progenitor but not distinguishable from the B6 progenitor. With the use of recombinant inbred strains derived from C3 and B6 progenitors, cosegregation analysis between inspiratory timing and measurements of lung volume and compliance indicate that strain differences in baseline breathing pattern and pressure-volume relationships are not genetically associated. Although strain differences in lung volume and compliance between C3 and B6 mice are inheritable, this study supports a dissociation between differential inspiratory time at baseline, a trait linked to a putative genomic region on mouse chromosome 3, and differential lung mechanics among C3 and B6 progenitors and their progeny.