FIGURE 1

Comparison of serum hAAT expression profiles obtained with different promoters. Mice (n = 5 mice per group) were injected at day 0 with 25 g plasmid carrying the hAAT gene directed by the indicated promoters: CMV (cytomegalovirus), EF1 (elongation factor 1), RSV (Rous sarcoma virus LTR), MTH (metallothionein), PGK (phosphoglycerate kinase), TTR (transthyretin), MoU3 (Moloney murine leukemia virus U3 region), eG3xAlb (albumin with upstream enhancer), DHFR (dihydrofolate reductase), Alb (albumin), and No (no promoter). Expression from the MTH promoter was induced in one of two groups injected with pBS.MTH-hAAT by adding ZnSO₄ (indicated by +) to the drinking water (25 mM final concentration). For all time points, the serum hAAT level relative to that of CMV is shown. Serum hAAT levels for pBS.CMV-hAAT were 5.6 10⁵, 3.6 10⁵, and 9.9 10² ng/ml at day 1, 7, and 122, respectively. For all promoters, hAAT expression levels did not change significantly after day 32; data from day 122 are shown. Mean relative values standard deviation are shown. The relative strength of all promoters, determined by serum hAAT levels at day 7 after injection relative to levels obtained with pBS.CMV-hAAT, is shown in the gray box. Based on the distribution of relative serum hAAT levels at day 7, CMV, EF1, MTH, PGK, TTR, DHFR, and Alb promoters (indicated by black bars) were selected for further studies. Serum hAAT was detected for pBS.No-hAAT only at day 1 after injection. Further details on the tested promoters are given in Table 2. ND, not detectable.