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

We have recently cloned the entire human elastin gene, including simil ar to 5.2 kilobases of the 5'-flanking sequences. To examine tissue-sp ecific expression of the elastin gene, we have developed a transgenic mouse line that expresses the human elastin promoter linked to the chl oramphenicol acetyltransferase (CAT) reporter gene. Assay of CAT activ ity in different tissues revealed the highest expression in the lungs and aorta, while lower levels were detected in the kidneys, heart, bra in, and skin; this distribution parallels the accumulation of elastin in developing animals. Comparison of CAT activity in the lungs of feta l (15-day gestation) and newborn (5-day postnatal) animals revealed si gnificantly (similar to 4-fold) higher activity in the fetal tissue. T he relatively high activity in the lungs progressively declined during the postnatal period up to 6 months. The promoter activity in the aor ta remained constant from 5 days to 3 months and then gradually declin ed, while in the skin, the activity peaked at 3 months, returning ther eafter to the control (5-day) level. Thus, there is evidence for devel opmentally regulated, tissue specific expression of the elastin promot er in vivo as tested in these transgenic mice.