Respiratory mechanics in mice: strain and sex specific differences

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Abstract
To assess the contribution of genetic background to respiratory mechanics, we developed a ventilator unit to measure lung function parameters in the mouse. We studied two commonly used inbred mice strains originating from Mus musculus domesticus (C57BL/6 and C3HeB/FeJ) and a third strain derived from Mus musculus molossinus [Japanese fancy mouse 1 (JF1)]. The ventilator allows for accurate performance of the different breathing manoeuvres required for measuring in‐ and expiratory reserve capacity, quasi‐static and dynamic compliance, and airway resistance. In combination with a mass spectrometer for monitoring gas concentrations, single‐breath manoeuvres were performed and He‐expirograms obtained, from which dead space volume and slope of phase III were determined. From each strain and each sex, 10, 2‐month old animals were studied immediately after being killed by an intraperitoneal overdose of xylazine and ketamine. C3HeB/FeJ and C57BL/6 exhibited comparable lung volumes. In male C3HeB/FeJ mice, e.g. vital capacity (VC) was 1072 ± 79 μL, inspiratory reserve capacity 782 ± 88 μL, and dead space volume at total lung inflation 216 ± 18 μL. Lung volumes of JF1 were significantly lower (e.g. VC 611 ± 53 μL, P < 0.01) even when normalized to body weight. In all three strains, specific lung volumes were significantly higher in females than in males, possibly explained by a higher oxygen demand during pregnancy and lactation, both of which fill most of their life times. Static compliance in C3HeB/FeJ was 64.3 ± 5.4 μL cmH2O–1. It was smaller in C57BL/6 and JF1 mice, even when related to the lung volume. Analysis of the degree of genetic vs. non‐genetic components of the phenotypic variation revealed that at least 80% of the total variation of lung volumes and static compliance in the mixed population is attributable to genetic differences between individuals. These differences will be verified in further studies by segregation and genetic linkage analysis.

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