Metallothionein-Human GH Fusion Genes Stimulate Growth of Mice

Abstract

The promoter or regulatory region of the mouse gene for metallothionein-I was fused to the structural gene coding for human growth hormone. These fusion genes were introduced into mice by microinjection of fertilized eggs. Twenty-three (70 percent) of the mice that stably incorporated the fusion genes showed high concentrations of human growth hormone in their serum and grew significantly larger than control mice. Synthesis of human growth hormone was induced further by cadmium or zinc, which normally induce metallothionein gene expression. Transgenic mice that expressed human growth hormone also showed increased concentrations of insulin-like growth factor I in their serum. Histology of their pituitaries suggests dysfunction of the cells that normally synthesize growth hormone. The fusion genes were expressed in all tissues examined, but the ratio of human growth hormone messenger RNA to endogenous metallothionein-I messenger RNA varied among different tissues and different animals, suggesting that expression of the foreign genes is influenced by site of integration and tissue environment.

Changes in Endogenous Growth Hormone Secretion and Onset of Puberty in Transgenic Rats Expressing Human Growth Hormone Gene.

“…In contrast, the day of vaginal opening advanced by 7-8 days hGH, and Line 2 had relatively low levels. Most mice expressing a transgene of GH from various species show an increase in growth rate [20]. In this study, transgenic rats secreting hGH at higher levels (Lane 1) had body weight increases that indicate a growth promoting effect of hGH on the rat.…”

“…GH producing cells (somatotorophs) in the pituitary disappear in transgenic mice secreting hGH [20]. It is also possible that low rGH levels in our transgenic rats were due to inhibition of somatotoroph proliferation.…”

“…Subsequently, the KpnI site was converted into a BamHI site by addition of BamHI linkers, leading to a EcoRI/BamHI vector fragment that contains a vector sequence and 5' flanking region of the mWAP gene. The coding region of the hGH gene was isolated as 2.1 kb BamHI/BamHI fragment from pMThGH [20] and was inserted into the BamHI site of the pBR327/5' WAP plasmid from which the protein coding region of mWAP gene was removed.…”

The acute promyelocytic leukemia PML-RARα protein induces hepatic preneoplastic and neoplastic lesions in transgenic mice

“…We report here inducible liver pathologies in transgenic mice expressing the PMLRARa protein driven by the mouse MT promoter. This promoter had been previously shown to e ciently direct transgene expression in a wide variety of murine tissues as well as to be inducible by heavy metals (Heisterkamp et al, 1990;Palmiter et al, 1983Palmiter et al, , 1985Crenshaw et al, 1987;Jhappan et al, 1990;Sandgren et al, 1990). Nine of the 10 founder mice lines resulting from MT-PMLRARa transgene injection were considered as nonexpressors.…”

The expression of the imprinted genes H19 and IGF-2 in choriocarcinoma cell lines. Is H19 a tumor suppressor gene?

“…Lanes 5 and 9 ± normal medium +2% FCS + 100 mg Zn 2+ (Figure 7, lanes 6 and 7). It was shown that 25 mM of ZnSO 4 in the drinking water can activate the metallothionein promoter in transgenic mice (Palmiter et al, 1983). However, Zn 2+ did not seem either to in¯uence the growth or the H19 expression level in the tumors that arose from original and transfected cells (Figure 6, lanes 2 and 3; Figure 7, lanes 2 and 3).…”