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Fig. 3. Abnormal ventilatory response of heterozygous mutants to hypoxia and hypercapnia. (A) Ventilatory tracings in one Phox2b^+/+ pup (top) and one Phox2b^lacZ/+pup (bottom). Both pups had similar baseline ventilation (air) and initial increase during hypoxia, but the Phox2b^lacZ/+ pup showed long post-hypoxic apneas (flat respiratory tracing). (B) Total duration of apneas (defined as respiratory pauses longer than twice the duration of the preceding breathing cycle) in air condition (3 minutes) and post-hypoxic condition (6 minutes). Apneas (0.7 and 2.8 apneas/minute in Phox2b^lacZ/+ mice; 0.8 and 2.8 apneas/minute in Phox2b^+/+ mice) were strikingly longer in Phox2b^lacZ/+ mice (^***P<0.001). Values are group means±s.e.m. (C) Ventilatory tracings in one Phox2b^+/+ pup (top) and one Phox2b^lacZ/+ pup (bottom). Both pups had similar baseline ventilation but the Phox2b^lacZ/+ pup showed a lower ventilatory response to hypercapnia. (D) The ventilatory increase during hypercapnia (three minutes) in Phox2b^lacZ/+ pups was about half that in Phox2b^+/+ pups, because of their lower increase in breathing frequency (not shown). ^*P<0.05; ^**P<0.01. Values are group means±s.e.m. (E) Ventilatory increase during hypercapnia at P10. The pups were exposed to 8% CO₂ for 5 minutes (instead of 3 minutes as in D) to examine possible changes in the time course of the hypercapnic response. No difference were observed between Phox2b^+/+ and Phox2b^lacZ/+ pups. Values are group means±s.e.m.

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