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Phenotyping Mouse Pulmonary Function In Vivo with the Lung Diffusing Capacity
Published on: January 6, 2015
Hypercapnic duty cycle is an intermediate physiological phenotype linked to mouse chromosome 5
H Schneider1, S P Patil, S Canisius
1Johns Hopkins Sleep Disorder, Division of Pulmonary and Critical Care Medicine, John Hopkins University School of Medicine, Baltimore, MD 21224, USA. hschnei3@jhmi.edu
Journal of Applied Physiology (Bethesda, Md. : 1985)
|June 10, 2003
Summary
Upper airway obstruction (UAO) increases the duty cycle (Ti/Tt) in normal individuals. Genetic factors influence this compensatory response, with specific genes on mouse chromosome 5 linked to Ti/Tt variations.
Area of Science:
- Physiology
- Genetics
- Respiratory Medicine
Background:
- Upper airway obstruction (UAO) can trigger compensatory breathing adjustments.
- The duty cycle (inspiratory time to total respiratory cycle length, Ti/Tt) is a key measure of respiratory effort.
- Genetic factors may influence the body's response to breathing challenges.
Purpose of the Study:
- To investigate if upper airway obstruction (UAO) leads to a compensatory increase in the duty cycle (Ti/Tt).
- To determine if genetic factors influence these compensatory Ti/Tt responses.
- To identify potential genetic linkages associated with Ti/Tt regulation in response to UAO and hypercapnia.
Main Methods:
- Examined Ti/Tt responses to UAO and hypercapnia in normal individuals.
- Assessed hypercapnia-induced Ti/Tt responses in different inbred mouse strains (C3H/HeJ and C57BL/6J) and their F2 offspring.
- Utilized F2 offspring data to perform genetic linkage analysis on the mouse genome.
Main Results:
- Normal individuals showed a significant increase in Ti/Tt during both hypercapnia and UAO compared to normal breathing.
- F2 offspring exhibited a significantly greater average Ti/Tt response to hypercapnia than their progenitor strains.
- Genetic linkage analysis identified a significant association between Ti/Tt response and an interval on mouse chromosome 5 (58-64 cM).
Conclusions:
- The duty cycle (Ti/Tt) serves as a physiological phenotype reflecting compensatory neuromuscular responses to maintain ventilation during UAO and hypoventilation.
- Genetic factors play a role in regulating the Ti/Tt response to breathing challenges.
- Candidate genes (Dagk4, Adrbk2, Nos1) on mouse chromosome 5 are implicated in the expression of sleep-disordered breathing.
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