Sexual dimorphism and growth hormone regulation of a hybrid gene in transgenic mice.
The sexually dimorphic expression of the urinary protein genes of mice (Mup genes) in the liver is mediated by the different male and female temporal patterns of circulating GH. Normal females were induced to male levels when GH was administered by injection to mimic the male GH pattern, showing that expression at the male level does not require a male sex steroid status in addition to intermittent GH. Two Mup-alpha 2u-globulin hybrid transgenes with different Mup gene promoters showed sexually dimorphic expression, and their expression in females increased to male levels upon testosterone treatment. GH-deficient (lit/lit) mice did not express these transgenes, and GH-deficient females did not respond to testosterone treatment, showing that GH was required for induction. Both normal and GH-deficient females were induced to male levels when GH was administered by injection. This is the first report of a transgene responsive to GH. A transgene consisting of a Mup promoter fused to a Herpes simplex virus thymidine kinase reporter sequence also showed sexual dimorphism, although to a lesser degree. It was expressed at the same level in normal females and GH-deficient mice of both sexes and was induced when GH-deficient mice were treated with GH. We propose that this transgene has a basal constitutive expression, possibly due to the absence of any rodent DNA downstream of the promoter. Since expression of the transgene was significantly induced by GH, the GH response is due at least in part to sequences in the promoter region.
al-Shawi
R
R
Agricultural and Food Research Council Centre for Genome Research, University of Edinburgh, United Kingdom.
Wallace
H
H
Harrison
S
S
Jones
C
C
Johnson
D
D
Bishop
J O
JO
D000510:Alpha-Globulins / Q000096:biosynthesis / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D005260:Female; D005786:Gene Expression Regulation; D013006:Growth Hormone / Q000502:physiology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011506:Proteins; D012727:Sex Characteristics
D000510:Alpha-Globulins; D011506:Proteins; C035737:major urinary proteins; D013006:Growth Hormone