Cryptic human growth hormone gene sequences direct gonadotroph-specific expression in transgenic mice.
Our laboratory reported previously that chimeric genes encoding either rat somatostatin (SS) or human GH (hGH), but containing the identical mouse metallothionein-I (MT) promoter/enhancer sequences and hGH 3'-flanking sequences, were selectively expressed in the gonadotrophs of transgenic mice. The experiments reported here were designed to identify the DNA sequences responsible for this unexpected cell-specific expression within the anterior pituitary. We produced new transgenic mice expressing fusion genes that tested separately the requirement of the MT or 3'-hGH sequences for gonadotroph expression. A fusion gene that retained the original MT and SS sequences, with a simian virus 40 polyadenylation signal exchanged for the 3'-hGH sequences, no longer directed strong pituitary expression, but was active in the liver. In contrast, a cytomegalovirus promoter/enhancer-SS-hGH fusion gene was expressed at the same high level in the anterior pituitaries of transgenic mice as the originally studied MT-SS-hGH gene. Immunohistochemical analysis indicated that pituitary expression of the cytomegalovirus promoter/enhancer-SS-hGH fusion gene was also restricted to gonadotroph cells in adult mice. These studies indicate that sequences within the 3'-flanking region of the hGH gene can direct expression of chimeric genes to pituitary cells that do not normally produce growth hormone.
Low
M J
MJ
Division of Molecular Medicine, New England Medical Center Hospital, Boston, Massachusetts 02111.
Goodman
R H
RH
Ebert
K M
KM
D000818:Animals; D006063:Chorionic Gonadotropin / Q000096:biosynthesis / Q000235:genetics*; D003001:Cloning, Molecular; D004274:DNA, Recombinant; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009928:Organ Specificity; D010957:Plasmids; D011401:Promoter Regions, Genetic; D015398:Signal Transduction; D013539:Simian virus 40 / Q000235:genetics; D013004:Somatostatin / Q000235:genetics*
D006063:Chorionic Gonadotropin; D004274:DNA, Recombinant; D013004:Somatostatin