TISSUE-SPECIFIC AND DEVELOPMENTALLY-REGULATED EXPRESSION OF HUMAN ELASTIN PROMOTER ACTIVITY IN TRANSGENIC MICE

We have recently cloned the entire human elastin gene, including similar to 5.2 kilobases of the 5'-flanking sequences. To examine tissue-specific expression of the elastin gene, we have developed a transgenic mouse line that expresses the human elastin promoter linked to the chloramphenicol acetyltransferase (CAT) reporter gene. Assay of CAT activity in different tissues revealed the highest expression in the lungs and aorta, while lower levels were detected in the kidneys, heart, brain, and skin; this distribution parallels the accumulation of elastin in developing animals. Comparison of CAT activity in the lungs of fetal (15-day gestation) and newborn (5-day postnatal) animals revealed significantly (similar to 4-fold) higher activity in the fetal tissue. The relatively high activity in the lungs progressively declined during the postnatal period up to 6 months. The promoter activity in the aorta remained constant from 5 days to 3 months and then gradually declined, while in the skin, the activity peaked at 3 months, returning thereafter to the control (5-day) level. Thus, there is evidence for developmentally regulated, tissue specific expression of the elastin promoter in vivo as tested in these transgenic mice.