Genetic control of differential inspiratory timing: Mechanical considerations

C. G. Tankersley, R. S. Fitzgerald, W. A. Mitzner, R. Rabold

Research output: Contribution to journalArticlepeer-review

Abstract

Inspiratory timing (TI) differences between C3H/HeJ (C3) and C57BL/6J (B6) inbred mice were shown to be genetically determined and linked to mouse chromosome 3. The present study examined 12 BXH recombinant inbred (RI) strains derived from C3 and B6 progenitors to consider phenotypes which cosegregate with TI. Breathing frequency (TTOT) and tidal volume (VT) were assessed on room air and during inspirate challenge (i.e. hypoxic and hypercapnic mixtures) using whole-body plethysmography. While TI/TTOT significantly (P < 0.01) varied with inspirate challenge, it remained constant among the BXH RI strains demonstrating cosegregation between TI and TTOT phenotypes in a challenge-specific manner. Mechanical considerations were further explored by performing quasistatic pressure-volume (PV) maneuvers. Relative to B6 mice, C3 mice demonstrated a significantly (P < 0.01) greater lung volume at airway pressures between 0 and 30 cmH2O. However, PV phenotypes among the BXH RI strains did not cosegregate with TI phenotypes. When considering minute ventilation (VE) as the product of TI/TTOT (i.e. the 'timer') and VT/TI (i.e. the 'driver'), these results suggested that variation in TI/TTOT was dependent on the inspirate challenge; i.e. the 'timer' was environmentally determined. Furthermore, genetic control of differential TI influenced between-strain variation in VE by affecting VT/TI. The differences in lung compliance between progenitor strains were not significant contributing factors.

Original languageEnglish (US)
Pages (from-to)A980
JournalFASEB Journal
Volume12
Issue number5
StatePublished - Mar 20 1998

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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