Abstract

The tight-skin (Tsk) mouse has recently been proposed as a genetic model of emphysema. In the present study, the development of emphysema was investigated in these mice with histological, biochemical, and ultrastructural methods at 4 days and at 1 and 2 months of life. At 4 days after birth, histological examination of the lungs revealed only a mild enlargement of the primary sacculi. Neither biochemical nor ultrastructural changes were seen however at this time. At 1 month of age, the histological examination showed marked emphysemalike changes, characterized by enlargement of air spaces accompanied by destruction of alveolar walls. Biochemical analysis showed a marked decrease in insoluble elastin content and a significant increase in salt-extractable collagen. Ultrastructural investigation revealed edema fluid in the interstitium and broken and disorganized elastic fibers. All these findings strikingly resemble the changes which occur in the lungs early after an instillation of elastase. In the 2-month-old Tsk mice the histological lesion progressed in severity. The ultrastructural findings were similar to those observed at 1 month, and the biochemical changes showed no signs of recovery. Thus, in these mice, the emphysematous lesion develops very rapidly between 4 days and 1 month of life and shows the characteristics of an elastolytic process which is still ongoing at 2 months of age.

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