TY - JOUR
T1 - Cryptic human growth hormone gene sequences direct gonadotroph-specific expression in transgenic mice
AU - Low, Malcolm J.
AU - Goodman, Richard H.
AU - Ebert, Karl M.
PY - 1989/12
Y1 - 1989/12
N2 - Our laboratory reported previously that chimeric genes encoding either rat somatostatin (SS) or human GH (hGH), but containing the identical mouse metallothionein-l (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. Immunohis-tochemical 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.
AB - Our laboratory reported previously that chimeric genes encoding either rat somatostatin (SS) or human GH (hGH), but containing the identical mouse metallothionein-l (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. Immunohis-tochemical 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=0024789874&partnerID=8YFLogxK
U2 - 10.1210/mend-3-12-2028
DO - 10.1210/mend-3-12-2028
M3 - Article
C2 - 2576462
AN - SCOPUS:0024789874
SN - 0888-8809
VL - 3
SP - 2028
EP - 2033
JO - Molecular Endocrinology
JF - Molecular Endocrinology
IS - 12
ER -