Stamm- und geschlechtsspezifische Unterschiede der Lungenarchitektur sowie der Ultrastruktur der Alveolarsepten bei C3H/HeJ- und JF1/Msf-Mäusen

Die Maus ist aufgrund ihrer guten Züchtbarkeit und leichten Handhabbarkeit eines der wichtigsten Labortiere in der pneumologischen Forschung. Die Inzuchtstämme bieten als Modellorganismus durch eine geringe genetische Variabilität eine wichtige experimentelle Quelle zur Untersuchung physiologischer,...

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Bibliographic Details
Main Author: Hühn, Dorothea
Contributors: Fehrenbach, Heinz (Prof.) (Thesis advisor)
Format: Doctoral Thesis
Published: Philipps-Universität Marburg 2008
Online Access:PDF Full Text
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Being easy to breed and to manage, the mouse is one of the most important animals used in pulmonary research. Inbred strains act as model organisms, due to their low genetic variability, an important experimental source to study physiological, pathophysiological and biochemical processes of mammalians (Paigen K 2000). It is necessary to characterise the phenotypes of commonly used transgenic animals and mutants as well as the frequently used inbred mouse strains. Knowledge about specific phenotypic properties eases the choice for a suitable laboratory animal (Reinhard C 2002). In several studies Reinhard et al. (2002; 2005) and Schulz et al. (2002) showed sex-specific differences in body weight, lung volume and functional parameters of the lung in between the inbred strains C3H/HeJ and JF1/Msf. They also demonstrated that C3H-mice have bigger body weight and lung volume and they found evidence that JF1-mice hold bigger alveolar diffusing capacity while having a smaller compliance related to body weight. The aim of this work was to examine whether morphologic correlatives in the ultrastructure could be found contributing to the differences in functional parameters of the lungs between the inbred strains and the sexes. The two different strains as well as sexes were compared. The selection of appropriate laboratory animals in future pulmonary research should be eased by the collection of data about the composition of the alveolar septum. Lungs of male and female mice of each strain (n=6 per group) were examined electron- and light-microscopically, based on stereological methods. The lunges were fixed via the trachea. The tissue blocks were osmicated, stained en bloc with tannic acid and uranyl acetate, embedded into araldite and Technovit and coloured. Volumes of parenchym, septums and airspace were identified on Richardson stained slices. Orcein stained slices were used to differentiate the airspace, to identify the alveolar surface area as well as the mean chord length as an indicator for the alveolar size and the mean face length as an indicator for the number of alveoli. The ultrastructure of the alveolar septums was analysed by electron microscopy, volume fractions of the components (alveolar epithel I and II, capillary endothel, interstitium with elastin and collagen) were quantified and the volumes were calculated. The results of this work gave explanations for strain and sex specific differences in the functional parameters and characteristics shown in prior studies between the two examined mouse-strains. JF1-mice compensated for the rather disadvantageous conditions for breathing, in comparison to the C3H-mice, caused by low specific compliance and high airway resistance, through a bigger gas exchange region, a thinner blood-gas barrier and a higher pulmonary diffusing capacity. At ultrastructural level there could not be found correlatives for the differences in the mechanics of breathing. Primarily there is an allometric connection between the differences of the lung volume and the volumes of the alveolar septum compartments. In the comparison of the strains, there is only a difference in the elastic and collagenous fibres, with the C3H-mice showing a proportionally higher amount of collagen and a lower amount of elastin than the JF1-mice. To give a plausible explanation for the lower specific compliance and the higher airway resistance the proportions would have had to be the other way around. The female animals had a higher gas exchange region than the male animals. This was especially within the C3H-strain, hardly within the JF1-strain. Causal for the bigger gas exchange region of female compared to male individuals when related to the body weight is primarily an evolutionary advantage to support reproduction. During pregnancy and lactation more energy in form of oxygen is needed. There is a difference in the structural parameters, although the mice in this study have never been pregnant or lactating. This means that during pregnancy and lactation not only new lung tissue has to be developed but the utilisation of existing tissue can be optimised. An important motivation for this work was to ease the choice of laboratory animals in pulmonary research. The data gathered regarding the volumes of elastin and collagen may be especially helpful in the future research of emphysema, if the examined strains are going to be used.