Fig. 2.
Disrupted breathing in Phox2b27Ala/+ mice. (A) Representative examples of plethysmographic recordings of wild-type (wt) and Phox2b27Ala/+ (ki) littermates breathing normal or hypercapnic air during the first 20 min after delivery. (B) Ventilatory (VE) tracings of Phox2b27Ala/+ (black dots) pups and their wild-type (white dots) littermates breathing air or hypercapnic mixture (8% CO2; shaded area). Periods of apnea and animals respirating mainly by gasps were excluded from the analysis. Each dot represents the mean ± SEM over a 30-sec period (n = 15 and n = 43 for mutant and wild-type pups, respectively) (when no bar is visible, it was smaller than the diameter of the dot). Baseline ventilation in air was depressed in the mutants, which did not increase VE during hypercapnia. Ventilation increased in both mutant and wild-type pups during the first 5 min in normal air because of increases in tidal volume and breathing frequency. Numerous mechanisms that operate immediately after delivery may account for this phenomenon. Among these mechanisms, the increase in lung compliance secondary to liquid resorption is accompanied by a progressive increase in tidal volume. Also in human infants, breathing becomes progressively more rapid and deeper after the first breaths (50). (C) Total apnea duration (sec) summed over the 5-min period in air for wild-type (n = 43) and Phox2b27Ala/+ (n = 15) pups, excluding those that respirated only by gasping (mean ± SEM). (D) Average VE for wild-type (n = 43) and Phox2b27Ala/+ (n = 15) pups breathing normal or hypercapnic air. Normocapnic values were calculated as the mean value over the first 5 min and the last 5 min of the recording to take into account the overall increase in VE. Hypercapnic VE values were calculated as the mean values over the last 3 min of hypercapnic exposure. In contrast to wild-type pups, the mutants did not significantly increase their ventilation in response to elevated pCO2.