Conclusion
In summary, we describe an efficient method for the identification and determination of biologic activity of novel ASV derived from the cell surface receptor genes. Sixty ASV were identified. The variants identified commonly include unique amino acids forming additional protein domains. Those ASV tested were shown to bind cognate ligand. An alternative splice variant derived from Tie1 (Tie1-751) was shown to bind not only Ang-1 but also cell surface Tie1 and Tie2. Using replication-deficient adenoviruses as a means of screening for biologic activity, we showed that RTK-derived ASV have selective potential therapeutic activity in a murine model of RA. Furthermore, we have shown for the first time that inhibition of the angiopoietin–Tie axis can markedly reduce arthritis severity. The present work demonstrates that ASV are a potential source of novel regulatory proteins, which may have therapeutic potential in animal models of disease and warrant testing in humans.