Genetic Control of Breathing: Effects of Gender and Lung Mechanics

Abstract

Robust genetic determinants regulate variation in breathing characteristics among inbred mouse strains. The current study investigates the role of lung structure and mechanics in affecting differences in breathing phenotypes. Baseline minute ventilation (VE) and breathing pattern (tidal volume, VT and frequency, f) were repeatedly measured in male and female C3H/HeJ (C3) and C57Bl/6J (B6) mice using plethysmography. Synchronized measurements of O2 consumption (VO2) and CO2 production (VCO2) were also measured. Quasistatic pressure-volume curves and respiratory impedance measurements characterized lung mechanical properties. The results suggest that VE, as referenced to the VO2 or VCO2 (Veq), in B6 mice is significantly (P < 0.05) greater than C3 mice. Moreover, VT and f correlated significantly (r-values = −0.74 and −0.78, P < 0.05) with lung elastance among all mice; however, these relationships were substantially greater in male (r-value = −0.83 and −0.92, P < 0.01) compared with female mice. In sum, robust genetic factors that regulate variation in breathing between C3 and B6 mice cosegregate with determinants of variable lung mechanical properties. Gender and variation in metabolic rate also modulate the genetic control of breathing in this model. NIA AG-21057 and NHLBI HL-010342