Differential control of ventilation among inbred strains of mice

Abstract

The role genetic factors play in ventilatory control was examined by challenging eight inbred strains of mice to acute hypercapnia under normoxic and hypoxic conditions. Age-matched mice were exposed for 3-5 min to inspired gases of the following composition (FICO2:FIO2) 0.03:0.10, 2) 0.03:0.21, 3) 0.08:0.10, and 4) 0.08:0.21, with intermittent room air exposures. Breathing frequency (f) and tidal volume (VT) of unanesthetized, unrestrained mice were assessed by whole body plethysmography. During room air breathing, significant (P < 0.01) interstrain differences were noted in the pattern, but minute ventilation (VE) did not differ among the strains. Relative to room air, mild hypercapnia with hypoxia (0.03:0.10) significantly (P < 0.01) elevated VE in each strain, and the percent increase in VE of the DBA/2J strain was significantly (P < 0.05) greater than the other strains. The ventilatory response to these conditions was achieved primarily by a significant (P < 0.01) increase in f among the strains. During severely hypercapnic normoxia (0.08:0.21) and hypoxia (0.08:0.10), the increase in VE was significantly (P < 0.01) greatest in the C57BL/6J (B6) mice and least in the C3H/HeJ (C3) mice. The difference in hypercapnic VE between B6 and C3 strains was largely due to a significantly (P < 0.01) greater increase in VT by B6 mice. On the assumption that environmental factors were identical, these data suggest that genetic determinants govern interstrain variation in the magnitude and pattern of breathing during hypoxia and hypercapnia. Moreover, hypoxic and hypercapnic ventilatory responses appear to be influenced by different genetic mechanisms.

TASK Channels Determine pH Sensitivity in Select Respiratory Neurons But Do Not Contribute to Central Respiratory Chemosensitivity

“…Regardless of genotype, all animals responded to hypercapnia with an increase in minute ventilation (i.e., the product of respiratory frequency and tidal volume). The increase in ventilation observed with elevated inspired CO 2 was similar to that measured in studies of other wild type mouse strains (Tankersley et al, 1994), and there was no significant . RTN neurons from TASK channel knock-out mice retain pH sensitivity and express a pH-sensitive K ϩ current like their wild-type counterparts.…”

Mice with Blunted Hypoxic Ventilatory Response are Susceptible to Respiratory Disturbance during Hypoxia

“…They found significant inter-strain differences in ventilation during air breathing and in the ventilatory response to two chemical loadings, and these inter-strain differences might have been influenced by genetic determinants. The present study seemed to support partly the study by Tankersley et al (1994). Several mouse strains of the present study were the same as those used in Tankersley's study, such as DBA/2, BALB/c, C3H/He, C57BL/6 and A/J.…”

“…However, as the mice recovered from apnea after air breathing or the heart beat was recognized by touching, the apneic episodes during severe hypoxic loading could be expected to have occurred independently of near arrest. Tankersley et al (1994) studied the interstrain variance of the ventilatory response to normal air, hypoxia and hypercapnia among eight inbred strains of mice. They found significant inter-strain differences in ventilation during air breathing and in the ventilatory response to two chemical loadings, and these inter-strain differences might have been influenced by genetic determinants.…”

“…However, to the best of our knowledge, there have been no reports showing that a blunted hypoxic ventilatory response is associated with respiratory disturbances, because it would be difficult to undertake this kind of investigation in a human study. Tankersley et al (1994) reported that there were differences in ventilatory behavior during exposure to hypoxia or hypercapnia among unanesthetized inbred mice, and suggested the presence of genetic influences on both responses. Therefore, it may be possible to identify mice strains with a blunted hypoxic ventilatory response by comparing the hypoxic ventilatory responses of inbred mice.…”

Inhaled aerosol particle dosimetry in mice: A review

“…Morphometric studies using mice are rare, but they have found significant differences in the airway morphometry of two murine strains with different genetic backgrounds (Oldham et al, 1994;Oldham and Robinson, 2007). Relevant differences in respiratory physiology have also been reported for different mouse strains and sexes (Tankersley et al, 1994;Reinhard et al, 2002;Flandre et al, 2003). In addition, structural and physiological alterations in mouse models of susceptibility as well as in genetically engineered mice may significantly influence inhaled particle deposition (Mall, 2008).…”