A SCANNING ELECTRON-MICROSCOPIC INVESTIGATION OF GENETIC EMPHYSEMA INTIGHT-SKIN, PALLID, AND BEIGE MICE, 3 DIFFERENT C57 BL 6J MUTANTS/

Three mutants of the C57 BL/6J strain, i.e., the tight-skin (Tsk), pal lid (pa), and beige (bg) mice have been reported to develop spontaneou s emphysema. However, the pathogenic mechanisms of this lesion may be different in the three mutants. Differences and similarities of these models were investigated by means of scanning electron microscopy. A l ight microscopic investigation provided the background for the SEM stu dy. C57 BL/6J (control), pa, Tsk, and bg mice were killed when they we re 1, 12, and 24 months old. At light microscopic investigation the lu ngs of the controls appeared normal at all ages. Those of the pa mice had normal appearance at 1 month, showed a few areas of air space enla rgement with destruction of alveolar septa at 12 months, and had a gen eralized enlargement of the air spaces associated with distortion of a lveolar septa at 24 months. The Tsk mice had a generalized panlobular emphysema at all ages. The lungs of the bg mice showed at all ages a g eneralized enlargement of the air spaces not accompanied by changes of the alveolar septa. At scanning electron microscopy the lung parenchy ma of control mice was essentially normal at all ages. Both alveolar d ucts and alveoli increased in size (the latter also in depth) with age . The number of interalveolar pores (Np) increased by 54% between 1 an d 12 months of age and by 49% between 12 and 24 months. The parenchyma of pa mice did not differ significantly from that of the controls at 1 month. At 12 months the alveoli appeared to be larger. At 24 months in some fields alveolar ducts were enlarged, the alveoli were also enl arged and very shallow. Np was not different from controls at 1 month but greater at 12 (+49%) and 24 (+26%) months. The parenchyma of Tsk m ice of all ages appeared distorted with enlargement of alveolar ducts and sacs and with alveoli with a large number of pores. These changes increased with age. Np was larger than the controls at all ages (+59% at 1 month, +119% at 12 months, and +80% at 24 months). The parenchyma of the bg mice of all ages appeared disorganized with large alveoli o f different shapes. There was a deterioration with age. No difference in Np was seen at any age between bg and control mice. Parenchymal cha nges characterized by distortion and enlargement of alveolar ducts and sacs were observed, even if with different onset and extent, in all m utants. However, an increase in Np, which is considered to represent t he early development of emphysema, was found only in Tsk and pa mice. In Tsk mice, high Np values were observed at all ages, whereas in pa m ice Np was increased only late in life when the pulmonary lesion devel ops. These differences indicate different pathogenetic mechanisms for these three mutants.