Developmental regulation of tropoelastin isoforms.

The production of tropoelastin isoforms was examined by cell-free translation of nuchal ligament RNA from cows of various ages ranging from 110 days of gestation to adult. Tropoelastin polypeptides synthesized in vitro were immunoprecipitated with a specific monoclonal antibody and separated by high resolution sodium dodecyl sulfate-polyacrylamide gel electrophoresis. From these experiments three distinct tropoelastin isoform patterns were detected at different developmental periods. 1) The fetal period was characterized by three polypeptides of about 67, 65, and 63 kDa produced in a ratio of 1:3:2. 2) In neonatal tissue, the same molecular mass forms were detected; however, the relative isoform ratio changed to 2:3:1. 3) From adult ligament RNA, only the 67- and 65-kDa forms of tropoelastin were detected, and these were produced in equal amounts. The pattern of tropoelastin isoforms produced from RNA isolated from other fetal elastic tissues was the same as for fetal ligament. Additional studies demonstrated that the relative amount of functional tropoelastin mRNA correlated with steady state levels of mRNA consistent with transcriptional regulation of tropoelastin synthesis. Although the significance of developmental switching of individual tropoelastin isoforms is unknown, it is likely that this process is required for proper assembly and, thus, function of elastic tissue.