Emphysema-like changes in the lungs of the blotchy mouse

The Blotchy allele is one of several mutations at the Mottled locus on the mouse X-chromosome. Affected males and heterozygous females within the several allelic groups possess varying degrees of connective tissue abnormalities similar to those found in copper-deficient and lathyritic animals, including aortic aneurysms and reduced skin tensile strength. There is evidence that defective inter- and intramolecular cross-links in collagen and elastin account for these abnormalities. The lung of the Blotchy mouse is also structurally and functionally abnormal. Hemizygous males have larger total lung volumes, markedly increased mean linear intercepts, and diminished internal alveolar surface area when compared to normal control animals. Light microsbopy and scanning electron microscopy show abnormal architecture with enlargement of air spaces and effacement of alveolar septa. Static air and saline pressure-volume curves show that lungs of Blotchy mice have decreased elastic recoil and are significantly more compliant than normal. These abnormalities in the lung of the Blotchy mouse suggest that the defects of the connective tissue proteins described in skin and aorta also involve the lung. The Blotchy strain may be a useful model in which to investigate how abnormalities of connective tissue proteins influence pulmonary structure and function.