Reorganization of pontine rhythmogenic neuronal networks in Krox-20 knockout mice.
We have shown previously that the inactivation of the zinc finger gene Krox-20 affects hindbrain segmentation, resulting in the elimination of rhombomeres 3 and 5. We demonstrate here that Krox-20 homozygous mutant mice exhibit abnormally slow respiratory and jaw opening rhythms, indicating that a modification of hindbrain segmentation influences the function of neuronal networks after birth. Central neuronal networks that control respiratory frequency are made predominantly depressant by the elimination of a previously undescribed rhythm-promoting system. Recordings of rhythmic activity from the isolated hindbrain following progressive tissue transections indicate that the reorganization takes place in the caudal pontine reticular formation. The newborn (PO) Krox-20-/- mice, in which apneas are ten times longer than in wild-type animals, may be a valuable model for the study of life-threatening apneas during early infancy.
Jacquin
T D
TD
Biologie Fonctionnelle du Neurone, Centre National de la Recherche Scientifique, Gif-sur-Yvette, France.
Borday
V
V
Schneider-Maunoury
S
S
Topilko
P
P
Ghilini
G
G
Kato
F
F
Charnay
P
P
Champagnat
J
J
D000818:Animals; D000831:Animals, Newborn; D001933:Brain Stem / Q000502:physiology; D002531:Cerebellum / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D051767:Early Growth Response Protein 2; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007231:Infant, Newborn; D051379:Mice; D009270:Naloxone / Q000494:pharmacology; D009415:Nerve Net / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D010920:Placenta / Q000502:physiology; D010991:Plethysmography; D011149:Pons / Q000502:physiology*; D011247:Pregnancy; D012119:Respiration / Q000187:drug effects / Q000502:physiology; D012127:Respiratory Distress Syndrome, Newborn; D013116:Spinal Cord / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D015017:Yolk Sac / Q000502:physiology; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; C497326:EGR2 protein, human; D051767:Early Growth Response Protein 2; C497327:Egr2 protein, mouse; D014157:Transcription Factors; D009270:Naloxone