Reorganization of Pontine Rhythmogenic Neuronal Networks in Krox-20 Knockout Mice

Abstract

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.

A human mutation in Phox2b causes lack of CO 2 chemosensitivity, fatal central apnea, and specific loss of parafacial neurons

“…Several mouse mutants with breathing defects that result from abnormal brainstem development and lead to neonatal death have been proposed as models to study the functional anatomy of the respiratory circuits. Egr2 Ϫ/Ϫ (27), Hoxa1 Ϫ/Ϫ (28), and Tlx3 Ϫ/Ϫ (29, 30) mice have extensive abnormalities in the pons and the medulla, and it may prove difficult to relate their phenotypes to a precise anatomical lesion. Impaired respiration in Phox2a Ϫ/Ϫ mice has been attributed to the loss of the LC (31), but atrophy of the gIX/X also may be involved (32).…”

Altered Respiratory Activity and Respiratory Regulations in Adult Monoamine Oxidase A-Deficient Mice

“…There is little information regarding the in vivo respiration of the adult mouse (Tankersley et al, 1997(Tankersley et al, , 1999. In addition, the availability of transgenic mice that present interesting mutations affecting the maturation and activity of respiratory network components (Erickson et al, 1996;Jacquin et al, 1996;Bou-Flores et al, 2000) is useful for analyzing the activity and regulations of respiration.…”

“…The ventilatory responses to hypoxia were studied by the whole-body plethysmography technique, as modified by Bartlett and Tenney (1970) and used repeatedly for studying breathing patterns in mice (Erickson et al, 1996;Jacquin et al, 1996;Tankersley et al, 1997Tankersley et al, , 1999. The animal chamber (200 ml), equipped with a temperature sensor (Checktemp 1, Hanna Instruments, Lingolsheim, France), was connected to a reference chamber of identical volume.…”

Cytoarchitecture of Pneumotaxic Integration of Respiratory and Nonrespiratory Information in the Rat

“…Many of these functions involve other dl-pons loci beyond the mPB-KF complex, such as the lateral parabrachial (lPB) nucleus, intertrigeminal nucleus (IT), and ventrolateral principal trigeminal sensory nucleus (Pr5). In addition, various subregions of the ventrolateral pons (vl-pons), such as the A5 noradrenergic neuron group and the lateral reticular formation, have been shown to modulate the respiratory rhythm (Jodkowski et al, 1994(Jodkowski et al, , 1997Jacquin et al, 1996;Borday et al, 1997). The variety of respiratory-related functions demonstrated in varying pontine loci suggests an extended organization of the pneumotaxic center in integrating multiplex physiological information.…”