GROWTH-RETARDATION IN RATS WHOSE GROWTH-HORMONE GENE-EXPRESSION WAS SUPPRESSED BY ANTISENSE RNA TRANSGENE

We produced four transgenic founder rats (F0) by introducing into rat embryos a fusion gene, which consisted of rat growth hormone (GH) prom oter containing with four copies of thyroid hormone response element ( TRE) and antisense cDNA sequences for rat GH. This transgene promoter directed 2.8-fold stimulation of CAT gene expression in transfected GH 3 rat pituitary tumor cells compared with the rat GH promoter alone. T wo of four transgenic rats expressed antisense RNA in the pituitary. T ransgenic offspring (F1) from each founder rat exhibited dwarfism at a s early as 3-4 weeks of age, and they exhibited approximately 70-85% r educed growth rate compared with their nontransgenic littermates over 56 weeks of observation. Plasma rat GH concentration was approximately 40-50% lower in transgenic F1 rats compared to their nontransgenic li ttermates. In these experiments, the pituitary hormone expression cont rolled in a complex manner was shown to be repressed by the antisense RNA transgene. Furthermore, the suppression of gene expression could b e achieved by antisense RNA transgene in the rat as well. (C) 1993 Wil ey-Liss, Inc.