Ventilatory responses to hypercapnia and hypoxia in heterozygous c-ret newborn mice.
The c-ret proto-oncogene encodes a tyrosine-kinase receptor involved in survival and differentiation of neural crest cell lineages. Previous studies have shown that homozygous c-ret-/- mice die soon after birth and have impaired ventilatory responses to hypercapnia. Heterozygous c-ret +/- mice develop normally, but their respiratory phenotype has not been described in detail. We used whole-body flow plethysmography to compare baseline breathing and ventilatory and arousal responses to chemical stimuli in unrestrained heterozygous c-ret +/- newborn mice and their wild-type c-ret +/+ littermates at 10-12 h of postnatal age. The hyperpnoeic and arousal responses to hypoxia and hypercapnia were not significantly different in these two groups. However, the number and total duration of apnoeas and periodic breathing episodes were significantly higher in c-ret +/- than in c-ret +/+ pups during hypoxia and post-hypoxic normoxia. These results are further evidence that respiratory control at birth is heavily dependent on genes involved in the neural determination of neural crest cells.
Laboratoire de Neurologie et Physiologie du Développement, Hôpital Robert-Debré, 48 Boulevard Sérurier, 75019, Paris, France.
Sophie
S
Aizenfisz
Stéphane
S
Dauger
Estelle
E
Durand
Guy
G
Vardon
Béatrice
B
Levacher
Michel
M
Simonneau
Vassilis
V
Pachnis
Claude
C
Gaultier
Jorge
J
Gallego
D000818:Animals; D000831:Animals, Newborn; D001049:Apnea / Q000235:genetics / Q000503:physiopathology; D029721:Drosophila Proteins; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006935:Hypercapnia / Q000235:genetics* / Q000503:physiopathology; D000860:Hypoxia / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D015656:Respiratory Mechanics / Q000235:genetics*
D029721:Drosophila Proteins; D011518:Proto-Oncogene Proteins; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila; C494999:Ret protein, mouse