High plasma levels of immunoreactive somatostatin in transgenic mice expressing a metallothionein-somatostatin fusion gene.

To test the hypothesis that processing of pre-prosomatostatin (pre-proSS) can be accomplished by cells that do not normally synthesize the precursor, we have introduced the rat pre-proSS gene under control of the mouse metallothionein promoter into the germ line of mice. Four of the 11 resultant transgenic mice had markedly elevated plasma levels of somatostatin-like immunoreactivity (SLI); however, their growth was identical to control littermates. Liver contained 263 +/- 89 pg of SLI/mg of protein and kidney had 152 +/- 19 pg/mg. Gel filtration chromatography of tissue extracts resolved one major 6000-dalton peak of SLI and three minor peaks of 8500, 3000, and 1600 daltons. The latter two corresponded in elution position to synthetic somatostatin-28 (S-28) and somatostatin-14 (S-14). Almost all of the plasma SLI corresponded in size to the 6000-dalton peptide. These findings indicate that a metallothionein-somatostatin fusion gene was successfully integrated into the mouse genome and was expressed in tissues that do not normally synthesize pre-proSS. Pre-proSS was processed to S-28 and S-14 but atypical processing to a 6000-dalton peptide also occurred.