Growth retardation in rats whose growth hormone gene expression was suppressed by antisense RNA transgene

Abstract

We produced four transgenic founder rats (F0) by introducing into rat embryos a fusion gene, which consisted of rat growth hormone (GH) promoter 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 GH3 rat pituitary tumor cells compared with the rat GH promoter alone. Two of four transgenic rats expressed antisense RNA in the pituitary. Transgenic offspring (F1) from each founder rat exhibited dwarfism at as early as 3-4 weeks of age, and they exhibited approximately 70-85% reduced 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 littermates. In these experiments, the pituitary hormone expression controlled in a complex manner was shown to be repressed by the antisense RNA transgene. Furthermore, the suppression of gene expression could be achieved by antisense RNA transgene in the rat as well.

Transgenic rainbow trout expressed sGnRH-antisense RNA under the control of sGnRH promoter of Atlantic salmon

“…However, in transgenic animals, the inhibitory effect of antisense RNA is seen to vary from complete failure (Munir et al 1990) to a 50% reduction in the level of target protein (Matsumoto et al 1993(Matsumoto et al , 1995. There are several mechanisms by which antisense RNA may exert its effects (Denhardt 1992), but the main inhibition of endogenous RNA is due to its destabilisation by antisense transcripts (Scherczinger et al 1992, Jiang et al 1994 The objectives of the present study were to try to antagonise the in vivo production of sGnRH in a transgenic line of rainbow trout through the transfer of a sGnRH-antisense construction driven by a specific salmon sGnRH Pab promoter (Klungland et al 1992b, Husebye et al 1997.…”

Functional expression of a Δ12 fatty acid desaturase gene from spinach in transgenic pigs

“…At birth, we performed a tail biopsy of each of the piglets. The integrity of the transgene was examined by Southern blotting analysis of genomic DNA extracted from the tail tissues (21). All animal procedures in the present study were approved by the Committee for Experimental Animals of Kinki University.…”

Effects of Exogenous Growth Hormone(GH)-Treatment on Carbon Tetrachloride(CCl4)-Induced Acute Liver Injury in GH-Deficient Mini Rats.

“…For example, retarded liver regeneration was observed after 70% partial hepatectomy (PH) in hypophysectomized rats, and this was recovered by the treatment of exogenous GH [1][2][3][4] . Mini rat (Jcl:Wistar-TgN (ARGHGEN) 1Nts) is a Wistar-derived transgenic strain in which pituitary GH is suppressed by the presence of antisense transgene for the rat GH located downstream of the GH gene 5,6 . The blood GH level of Mini rats is approximately 60 to 80 % of that of Wistar rats, and the body weight gain is significantly suppressed compared with that in age-matched Wistar rats 5,6 .…”

“…Mini rat (Jcl:Wistar-TgN (ARGHGEN) 1Nts) is a Wistar-derived transgenic strain in which pituitary GH is suppressed by the presence of antisense transgene for the rat GH located downstream of the GH gene 5,6 . The blood GH level of Mini rats is approximately 60 to 80 % of that of Wistar rats, and the body weight gain is significantly suppressed compared with that in age-matched Wistar rats 5,6 . The difference in the responses to chemical-induced hepatic injury between Mini rats and Wistar rats was reported by several researchers [7][8][9][10][11][12][13][14] .…”