Differential lung mechanics are genetically determined in inbred murine strains

Abstract

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 cmH2O, lung volumes are significantly (P < 0.01) greater in C3 mice relative to the B6 and A/J strains. In addition, the B6C3F1/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.

Lung structure phenotype variation in inbred mouse strains revealed through in vivo micro-CT imaging

“…The total mean and standard error (SE) volume of the lungs of the C57BL/6, A/J, and BALB/c mice was 992.5 (Ϯ39.7) l, 965.5 (Ϯ50.2) l, and 1,152.5 (Ϯ62.5) l. A statistical comparison of the mean lung volumes among the strains was completed using a oneway ANOVA followed by Tukey's test for the pairwise comparison of means between the strains and it was found that with the current sample size there were no significant differences in calculated lung volume between the three strains of mice at a positive airway pressure of 20 cmH 2 O. Comparable values for inter-strain lung volumes and intra-strain variation for lung volume and have been reported for the C57BL/6 and A/J strains (15,23,27).…”

Altered Upper Airway and Soft Tissue Structures in the New Zealand Obese Mouse

“…We did not measure functional residual capacity in our studies, although this measurement can be obtained noninvasively using sophisticated micro-CT methods (54) or complex plethysmography (55). As Tankersley and colleagues have shown (56), differences in lung mechanics are found in different mouse strains. Thus, we cannot exclude the possibility that upper airway changes in the obese NZO mouse are at least partially due to reduced functional residual capacity.…”

Force Fluctuation induced Relengthening of Acetylcholine-contracted Airway Smooth Muscle

“…The A/J mouse strain is more hyperresponsive (modeling innate airway hyperresponsiveness, if not asthma) compared with the C57Bl/6J strain (12)(13)(14)(15). Anesthetized mice underwent tracheostomy, and were ventilated with a computer-controlled small-animal ventilator (flexiVent; SCIREQ, Montreal, Canada).…”