Different respiratory control systems are affected in homozygous and heterozygous kreisler mutant mice

Abstract

During embryonic development, restricted expression of the regulatory genes Krox20 and kreisler are involved in segmentation and antero‐posterior patterning of the hindbrain neural tube. The analysis of transgenic mice in which specific rhombomeres (r) are eliminated points to an important role of segmentation in the generation of neuronal networks controlling vital rhythmic behaviours such as respiration. Thus, elimination of r3 and r5 in Krox20–/– mice suppresses a pontine antiapneic system (Jacquin et al., 1996). We now compare Krox20–/– to kreisler heterozygous (+/kr) and homozygous (kr/kr) mutant neonates. In +/kr mutant mice, we describe hyperactivity of the antiapneic system: analysis of rhythm generation in vitro revealed a pontine modification in keeping with abnormal cell specifications previously reported in r3 (Manzanares et al., 1999b). In kr/kr mice, elimination of r5 abolished all +/kr respiratory traits, suggesting that +/kr hyperactivity of the antiapneic system is mediated through r5‐derived territories. Furthermore, collateral chemosensory pathways that normally mediate delayed responses to hypoxia and hyperoxia were not functional in kr/kr mice. We conclude that the pontine antiapneic system originates from r3r4, but not r5. A different rhythm‐promoting system originates in r5 and kreisler controls the development of antiapneic and chemosensory signal transmission at this level.

Ion Channel Development, Spontaneous Activity, and Activity-Dependent Development in Nerve and Muscle Cells

“…At E12.5 lowfrequency activity synchronized between different nerve roots was recorded, with a slightly longer interepisode interval than the more caudal lower frequency events at E10.5 (interval of 75 s; Refs. 1,98,99). The activity at E12.5 is similar to that seen in chick stage 24, and in both animals this is recorded soon after the disappearance of the rhomobomere boundaries.…”

“…Extracellular motor root recordings [in elevated external K ϩ (8 mM)] in chick hindbrain branchiomeric nerves did not show any activity until stage 24, when periodic episodes of activity were observed with an interval rate of ϳ1 min (averaged over stages 24 -26) (98,99,183). These changed over developmental time (up to stage 36), with more bursts of activity in each episode, with the interval between episodes lengthening to 2.4 min.…”

Respiratory Adaptations to Lung Morphological Defects in Adult Mice Lacking Hoxa5 Gene Function

“…Furthermore, transcriptional regulators for Hox gene expression, such as Krox20 and kreisler, were shown to be implicated in the control of breathing (41)(42)(43). Both Krox20 and kreisler genes are involved in hindbrain segmentation and their loss of function results in distinct respiratory phenotypes associated with defects of central components of the respiratory control system (44,45). Unlike Hox mutants in which abnormal hindbrain segmentation causes respiratory defects, the respiratory activity of Hoxa5 -/-mice is rhythmic and regular.…”

Vesicular Glutamate Transporter 2 Is Required for Central Respiratory Rhythm Generation But Not for Locomotor Central Pattern Generation

“…The pressure difference between the two chambers was measured with a differential pressure transducer (DP-103-10; Validyne, Northridge, CA) connected to sine wave demodulator (CD15; Validyne). The spirogram was stored on a personal computer (PC) (Chatonnet et al, 2002). Calibrations were made during each recording session by injecting 5 l of air into the experimental chamber with a Hamilton syringe.…”