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Measuring the lung function in the mouse: the challenge of size.

Irvin CG, Bates JH - Respir. Res. (2003)

Bottom Line: Measurement of the effects of drugs, mediators and infectious agents on various models of lung disease, as well as assessment of lung function in the intact mouse has the potential for significantly advancing our knowledge of lung disease.Because of compromises made between precision and noninvasiveness, data obtained may have an uncertain bearing on the mechanical response of the lung.These advances, resulting in our current ability to measure sophisticated indices of lung function in laboratory animals, are likely to lead to important insights into the mechanisms of lung disease.

View Article: PubMed Central - HTML - PubMed

Affiliation: Vermont Lung Center, Department of Medicine, College of Medicine, University of Vermont, Room 226, HSRF, 149 Beaumont Avenue, Burlington, VT 05405, USA. Charles.Irvin@uvm.edu

ABSTRACT
Measurement of the effects of drugs, mediators and infectious agents on various models of lung disease, as well as assessment of lung function in the intact mouse has the potential for significantly advancing our knowledge of lung disease. However, the small size of the mouse presents significant challenges for the assessment of lung function. Because of compromises made between precision and noninvasiveness, data obtained may have an uncertain bearing on the mechanical response of the lung. Nevertheless, considerable recent progress has been made in developing valid and useful measures of mouse lung function. These advances, resulting in our current ability to measure sophisticated indices of lung function in laboratory animals, are likely to lead to important insights into the mechanisms of lung disease.

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Photomicrograph of the parenchyma and respiratory bronchioles of a mouse (20 gram female BALB/c) lung. Note the rapid branching from a conducting airway into alveolar ducts and the relatively large airways. Stain is H & E with 5 × magnification.
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Figure 1: Photomicrograph of the parenchyma and respiratory bronchioles of a mouse (20 gram female BALB/c) lung. Note the rapid branching from a conducting airway into alveolar ducts and the relatively large airways. Stain is H & E with 5 × magnification.

Mentions: One look through the microscope at a section of mouse lung (Figure 1) demonstrates that the mouse lung is considerably different in structure from the human lung, although relatively little has been published about the architecture of the mouse lung compared to other species. What is known about the structure of the mouse lung probably has important bearing on its function [12-14]. The total lung capacity (TLC) of the mouse is about 1 ml compared to 10 ml of the rat and 6,000 ml of a human. Like the human, there are 5 lobes in the right mouse lung, but unlike the human the mouse has only a single left lung. Also unlike the human lung, but similar to the rat, the mouse pleura is thin, yet it is strong enough to be inflated to considerably higher pressures than the 30 cm H2O normally associated with TLC (W Mitzner, personnel communications). The parenchyma of the mouse lung occupies a smaller fraction of the total lung than that of the rat but more than that of the human (mouse: 18%, rat: 24%, human: 12% lung volume). The alveoli of the mouse lung are smaller (80 μm mean linear intercept (MLI)) than those of the rat (MLI 100 μm) or human (MLI 210 μm). The blood-gas barrier thickness in the mouse (0.32 μm) is similar to that of the rat (0.38 μm) but somewhat smaller than that of the human (0.62 μm), which might have important implications for both gas exchange and parenchymal lung mechanics. The airways constitute a large percentage of the lung in mice (11%) compared to rats (5.7%). Cartilage is present in the mouse trachea but is less well organized than in other species; only the upper part of the trachea has the complete rings seen in other mammals and these rapidly change to plates as one proceeds distally. Mouse lungs have fewer respiratory bronchioles and airway generations (13–17 generations) than do human lungs (17–21 generations) with the airways of the mouse lung exhibiting a monopodial as opposed to dichotomous branching pattern. Two other significant features of the mouse lung are the thinness of the respiratory epithelium and the relatively large airway lumen [12,14]. This large airway caliber is speculated to reduce the flow-resistive load that would otherwise result from the rapid respiratory rate (250–350 bpm) required by the mouse to maintain body temperature [15]. An important functional difference between mice and rats compared to humans is the paucity, or even complete absence, of submucosal glands and the presence of high numbers of Clara cells [12]. Exactly what significance all these anatomical features of the mouse lung have for lung function is speculative, but it has been our experience that the baseline airway resistance of mice that have been sensitized and challenged with antigen differs imperceptibly from that of control animals [16,17]. This suggests that inflammatory processes that could compromise lung function in larger animals (e.g. humans) might have little effect in mice because of their relatively large airway size and/or lack of mucous glands.


Measuring the lung function in the mouse: the challenge of size.

Irvin CG, Bates JH - Respir. Res. (2003)

Photomicrograph of the parenchyma and respiratory bronchioles of a mouse (20 gram female BALB/c) lung. Note the rapid branching from a conducting airway into alveolar ducts and the relatively large airways. Stain is H & E with 5 × magnification.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC184039&req=5

Figure 1: Photomicrograph of the parenchyma and respiratory bronchioles of a mouse (20 gram female BALB/c) lung. Note the rapid branching from a conducting airway into alveolar ducts and the relatively large airways. Stain is H & E with 5 × magnification.
Mentions: One look through the microscope at a section of mouse lung (Figure 1) demonstrates that the mouse lung is considerably different in structure from the human lung, although relatively little has been published about the architecture of the mouse lung compared to other species. What is known about the structure of the mouse lung probably has important bearing on its function [12-14]. The total lung capacity (TLC) of the mouse is about 1 ml compared to 10 ml of the rat and 6,000 ml of a human. Like the human, there are 5 lobes in the right mouse lung, but unlike the human the mouse has only a single left lung. Also unlike the human lung, but similar to the rat, the mouse pleura is thin, yet it is strong enough to be inflated to considerably higher pressures than the 30 cm H2O normally associated with TLC (W Mitzner, personnel communications). The parenchyma of the mouse lung occupies a smaller fraction of the total lung than that of the rat but more than that of the human (mouse: 18%, rat: 24%, human: 12% lung volume). The alveoli of the mouse lung are smaller (80 μm mean linear intercept (MLI)) than those of the rat (MLI 100 μm) or human (MLI 210 μm). The blood-gas barrier thickness in the mouse (0.32 μm) is similar to that of the rat (0.38 μm) but somewhat smaller than that of the human (0.62 μm), which might have important implications for both gas exchange and parenchymal lung mechanics. The airways constitute a large percentage of the lung in mice (11%) compared to rats (5.7%). Cartilage is present in the mouse trachea but is less well organized than in other species; only the upper part of the trachea has the complete rings seen in other mammals and these rapidly change to plates as one proceeds distally. Mouse lungs have fewer respiratory bronchioles and airway generations (13–17 generations) than do human lungs (17–21 generations) with the airways of the mouse lung exhibiting a monopodial as opposed to dichotomous branching pattern. Two other significant features of the mouse lung are the thinness of the respiratory epithelium and the relatively large airway lumen [12,14]. This large airway caliber is speculated to reduce the flow-resistive load that would otherwise result from the rapid respiratory rate (250–350 bpm) required by the mouse to maintain body temperature [15]. An important functional difference between mice and rats compared to humans is the paucity, or even complete absence, of submucosal glands and the presence of high numbers of Clara cells [12]. Exactly what significance all these anatomical features of the mouse lung have for lung function is speculative, but it has been our experience that the baseline airway resistance of mice that have been sensitized and challenged with antigen differs imperceptibly from that of control animals [16,17]. This suggests that inflammatory processes that could compromise lung function in larger animals (e.g. humans) might have little effect in mice because of their relatively large airway size and/or lack of mucous glands.

Bottom Line: Measurement of the effects of drugs, mediators and infectious agents on various models of lung disease, as well as assessment of lung function in the intact mouse has the potential for significantly advancing our knowledge of lung disease.Because of compromises made between precision and noninvasiveness, data obtained may have an uncertain bearing on the mechanical response of the lung.These advances, resulting in our current ability to measure sophisticated indices of lung function in laboratory animals, are likely to lead to important insights into the mechanisms of lung disease.

View Article: PubMed Central - HTML - PubMed

Affiliation: Vermont Lung Center, Department of Medicine, College of Medicine, University of Vermont, Room 226, HSRF, 149 Beaumont Avenue, Burlington, VT 05405, USA. Charles.Irvin@uvm.edu

ABSTRACT
Measurement of the effects of drugs, mediators and infectious agents on various models of lung disease, as well as assessment of lung function in the intact mouse has the potential for significantly advancing our knowledge of lung disease. However, the small size of the mouse presents significant challenges for the assessment of lung function. Because of compromises made between precision and noninvasiveness, data obtained may have an uncertain bearing on the mechanical response of the lung. Nevertheless, considerable recent progress has been made in developing valid and useful measures of mouse lung function. These advances, resulting in our current ability to measure sophisticated indices of lung function in laboratory animals, are likely to lead to important insights into the mechanisms of lung disease.

Show MeSH
Related in: MedlinePlus