DEVELOPMENT OF TRANSGENIC XENOPUS-LAEVIS WITH A HIGH C-SRC GENE-EXPRESSION

Xenopus laevis larvae with an elevated expression of c-src were genera ted by mating a transgenic X. laevis male frog carrying proviral Rous sarcoma virus (RSV) long terminal repeat (LTR) and most of the pol gen e sequences in its sperm DNA and a normal X, laevis female frog. Offsp ring (15-20%) with a higher dosage of c-Src, detected in disorganized myotomal musculature and in cerebral and spinal neuronal cells by immu nohistochemical analysis, developed abnormally, with edemas (in most c ases), head deformities, and eye and axial system defects. In the rema ining embryos, a small increase in c-src expression seemed to be compa tible with normal embryogenesis. The dosage of c-Src correlated with t he dosage of RSV LTR integrated in frog DNA as revealed by Southern an d polymerase chain reaction (PCR) analyses. Authenticity of the integr ated RSV LTR including enhancer sequence was proved by sequencing. Pro bing of total RNA from aberrant larvae demonstrated several times high er dosage of c-src mRNA in their tissues than in control tadpoles. We hypothesize that the integrated RSV regulatory sequences can stimulate the expression of c-sre proto-oncogene of X. laevis above a treshold that interferes with the early developmental program of frog embryos. Mel. Reprod. Dev. 50,410-419, 1998. (C) 1998 Wiley-Liss, Inc.