Respiratory mechanics in mice: strain and sex specific differences

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 microL, inspiratory reserve capacity 782 +/- 88 microL, and dead space volume at total lung inflation 216 +/- 18 microL. Lung volumes of JF1 were significantly lower (e.g. VC 611 +/- 53 microL, 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 microL 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.

A transgenic mouse with vascular endothelial over-expression of the non-muscle myosin light chain kinase-2 isoform is susceptible to inflammatory lung injury: role of sexual dimorphism and age

“…Furthermore, as several acute and chronic inflammatory pulmonary disorders, which include ALI and acute respiratory distress syndrome (ARDS), are influenced by gender, [ 13 ], [ 14 ], [ 15 ], [ 16 ], [ 17 ], [ 18 ], [ 19 ], [ 20 ], [ 21 ] and [ 22 ] age, [ 23 ], [ 24 ], [ 25 ], [ 26 ] and [ 27 ] or gender-age interactions, [ 28 ], [ 29 ] and [ 30 ] we designed our study to evaluate the influence of these comodifiers on postulated nmMLCK2-mediated increases in vascular paracellular transport. This is supported by findings in mice, which like humans, have varying respiratory properties that differ between sexes [ 31 ], [ 32 ] and [ 33 ] and with age, [ 34 ] and [ 35 ] information often neglected when describing a pulmonary phenotype.…”

“…6 The gene also encodes a ~19-kDa protein known as kinase-related protein (KRP) or telokin that is transcribed from the C-terminal exons [30][31][32][33], and it serves to stabilize actin filaments. 7 In addition to smooth muscle myosin light chain kinase (smMLCK) and KRP, 5 splice variants were identified that use the start codon of the 210-kDa isoform, but they have internal exon deletions compared with the longest variant (nmMLCK1).…”

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

“…Phenotyping the lung function in the mouse has revealed strain specific differences between parameters such as lung volumes, compliance of the lung, respiratory system resistance, and ventilatory responses (10,15,19,21,(25)(26)(27), to name a few. However, as reported by Reinhard et al (19), there is no direct evidence that any one strain exhibits directly correlated relationships between lung function parameters, which suggests that they are not necessarily coinherited.…”

Morphometric Deformations of Small Airways and Alveoli under Quasi-static Inflation Process

“…5) (Schulz et al, 2002). Figure 6 shows the airway deformations of control and asthma model mouse at FRC and VT. At FRC, the diameter was larger in asthma group than in control group.…”

“…FRC (functional residual capacity) was defined as the lung volume at euthanasia, and the lung volume could be externally regulated using a syringe connected to the trachea. The volume of TV (at end of tidal inspiration) and TLC (total lung capacity) was defined as the sum of FRCϩ250 and 800 mL, respectively (Schulz et al, 2002).…”