Fig. 1.
Loss of ISM1 leads to pulmonary emphysema in mice. (A) Hematoxylin and eosin (H&E) stained left lungs and (B) mean linear intercepts (MLI) of FVB/NTac WT and Ism1−/− mice at 1, 2, 6, and 9 mo of age. (C) Whole-mount stereoscopic elastin/collagen-labeled left lungs of FVB/NTac WT and Ism1−/− mice at 6 mo of age. (D) H&E stained left lung of FVB/NTac Ism1+/− mice at 9 mo of age. (E) MLI of FVB/NTac WT, Ism1+/−, and Ism1−/− mice at 9 mo of age. (F) ISM1 protein level in FVB/NTac WT, Ism1+/−, and Ism1−/− lungs at 2 mo of age determined by enzyme-linked immunosorbent assay. (G) Pathology grading of emphysema in FVB/NTac WT, Ism1+/−, and Ism1−/− mice at 2 mo of age. (H–O) Spirometry of FVB/NTac WT and Ism1−/− mice at 2 mo of age. (H) Total lung capacity, (I) functional residual capacity, (J) residual volume, (K) static compliance, (L) dynamic compliance, (M) forced expiratory volume at 100 ms (FEV100), (N) Tiffeneau–Pinelli index (FEV100/FVC), and (O) airway resistance. Data are mean ± SD and were analyzed by two-group, two-tailed Student’s t test (B and H–O), and one-way ANOVA with Tukey’s post hoc test (E and F). *P < 0.05, **P < 0.01, ***P < 0.001, and ****P < 0.0001. n = 3 to 7 mice per group. (Scale bars, 200 μm for A, C, and D.) Data from A and B are integrated from two independent experiments (biological repeats, n = 7) except for MLI data for 1- and 6-mo-old mouse groups, which are from one independent experiment (n = 4). Data from C–G are independent experiments using different WT and Ism1−/− mice. Data from H–O are independent experiments using the same WT and Ism1−/− mice.