TUMORS INDUCED BY DEREGULATED EXPRESSION OF SH2 AND SH3 DOMAINS OF CHICKEN C-YES IN TRANSGENIC MICE

Numerous in vitro studies have revealed that the Src homology 2 (SH2) and Src homology 3 (SH3) domains play critical roles in signal transdu ction processes, However, the functions and significance of these doma ins in vivo remain largely unknown, To understand the role that these domains may play in vivo, we produced transgenic mice that carry an am ino-terminal 1.1 kb fragment of chicken c-Yes containing SH2 and SH3 d omains, under transcriptional control of murine sarcoma virus (MSV) lo ng terminal repeat sequences (LTR), We found that mice from several di fferent transgenic Lines developed liver tumors, lung tumors, and rena l dysplasia, Expression of the transgene in tumor tissues was demonstr ated by RT-PCR, Thus, tumorigenesis in our transgenic mice appears to be the results of perturbed signal transduction processes by deregulat ed expression of SH2 and SH3 domains.