Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034067 (emphysema)
 11,506 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inheritance of the Blotchy allele at the X-chromosomal Mottled locus of mice results in changes in the lung which resemble emphysema. Previous studies using measurements of mean linear intercept have recognized emphysema in the hemizygous, Blo/Y, male and homozygous, Blo/Blo, female, but not in the heterozygous, Blo/+, female. The aim of this study was to develop a rapid, accurate method for analysis of emphysema and to establish whether it would identify emphysema in the heterozygote. Lungs from wild type and outbred Blo mice were inflated with fixative at a pressure of 25 cm and then sectioned and stained. Transect lengths across air spaces were measured using computerized image analysis and the results were plotted as histograms. Data were also expressed as cumulative frequencies (ogives) and subjected to statistical analysis by the non-parametric Kolmogorov-Smirnov test. Emphysema was shown by significantly increased (P less than 0.001) transect lengths in the Blo/Blo female and Blo/Y male compared with the wild type controls. The heterozygous Blo/+ mice form an intermediate group significantly different (P less than 0.001) from the wild and blotchy mice. The sensitivity of the method is illustrated by the fact that the Blo/+ female formed an intermediate group between wild type and the Blo/Y male and Blo/Blo female.
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PMID:Emphysema in the Blotchy mouse: a morphometric study. 319 4

Male mice with the sex-linked mutation Blotchy (Blo) have a defect in copper metabolism which results in deficient activity of a number of copper-containing enzymes. Inbred Blo/y mice spontaneously develop lung abnormalities which resemble emphysema and often die of ruptured aortic aneurysm. Lung, tail tendon, and tibial bone collagens from inbred Blo/y and their normal (+/y) litter mates were reduced with standardized [3H]NaBH4, acid and alkaline hydrolyzed, and chromatographed in order to quantify the aldehydic crosslink precursors, and the labile reducible and nonreducible stable mature covalent intermolecular crosslinks. Reducible lung collagen crosslinks were markedly (60%) decreased in the Blo/y mice and few, if any, mature nonreducible crosslinks were present. Total aldehydes were also decreased (65%) when Blo/y was compared to +/y. In tail tendon and bone, collagen crosslinks were decreased by only 28% and 15%, respectively. Selectively severe lack of activity of the copper-dependent enzyme level oxidase in lung with only partial lack in tendon and bone could account for the results obtained. Alternatively, insufficient reducible crosslinks, coupled with increased collagen turnover in the lung could prevent formation of the more mature stable crosslinks required to provide a proper connective tissue framework for the Blo/y lung.
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PMID:Structural crosslinking of lung connective tissue collagen in the blotchy mouse. 356 65

Blotchy is an X-linked recessive mutation at the "Mottled" locus in the mouse. The affected blotchy male (Blo/Y) mouse from an inbred genetic background demonstrates morphologic and physiologic abnormalities consistent with emphysema in adult life. Breeding of Blo/Y mice has been difficult because the inbred Blo/Y males are sterile. We report the successful development of a line of outbred Blo/Y male and Blo/Blo female nice by the controlled outcross mating of the inbred heterozygous Blo/+ female with the Argonne hybrid B6CF1 male mouse. The subsequent outcross Blo/Y progeny breed vigorously with the outcrossed Blo/+ female. The lungs of the outbred Blo/Blo female and inbred Blo/Y male mice demonstrate mild to moderate panacinar emphysema with a significant decrease in internal surface area (p less than 0.005) and an increase in mean linear intercept (p less than 0.005). In contrast, the lungs of the outbred Blo/Y is structurally normal. Despite the absence of emphysema-like changes in the outbred Blo/Y males, there were phenotypic features that suggest inherited abnormalities in connective tissue proteins including 1) high incidence of aortitis leading to premature death from aneurysmal rupture, and 2) significant decrease in the morphometrically determined parenchymal elastic fiber length in the lung (p less than 0.01). The outbred blotchy strain may be a useful experimental animal model in determining the pathogenesis of emphysema.
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PMID:Morphologic and phenotypic analysis of an outcross line of blotchy mouse. 686 19