Expression of the beta subunit of chorionic gonadotropin in transgenic mice.
Transcriptional activation of the chorionic gonadotropin (CG) genes is linked to trophoblast differentiation. In a multistep process, cytotrophoblasts expressing only the alpha subunit differentiate into intermediates that coexpress the CG beta subunit. To study the regulation of expression of the CG beta genes in vivo, we constructed mice carrying a 36-kilobase cosmid insert containing the six CG beta genes. In the placenta of all three constructed lines, expression occurred at approximately 1% of the levels in first trimester human placenta. The amount of CG beta mRNA in mouse placenta was a function of gestational age; however, in contrast to the human placenta where CG beta peaks early in pregnancy, CG beta transcripts were only detectable in the mouse placenta late in gestation, i.e. from day 14 onward. Human CG beta was expressed also in cerebral cortex, pituitary, and at minute levels in adrenal. Pituitary CG beta expression was significantly lower than in placenta. Unexpectedly, transcripts were observed in cerebral cortex at levels comparable with the placenta. Most of the CG beta transcripts in mouse placenta are derived from CG beta genes 5, 3, and 8, in a ratio similar to that found in human placenta. In contrast, only CG beta genes 1 and 2 were transcribed in transgenic mouse brain; open reading frames from the CG beta 1 and beta 2 transcripts differ substantially from the CG beta protein. The data show that although the mouse lacks a CG beta-like gene, the human CG beta genes are transcribed in a regulated fashion in mouse placenta. Moreover, the stage-specific induction of the transgene suggests that mouse placental cells may express CG beta in an intermediate cell comparable with that seen in human placenta. Taken together, these data suggest that transgenic mice can be used as a model for elucidating the mechanisms involved in regulated expression of the CG beta gene cluster in vivo. Additionally, a different subset of CG beta genes (CG beta 1 and beta 2) is active in the mouse brain.
Strauss
B L
BL
Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, Missouri 63110.
Pittman
R
R
Pixley
M R
MR
Nilson
J H
JH
Boime
I
I
D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D001921:Brain / Q000378:metabolism; D006063:Chorionic Gonadotropin / Q000096:biosynthesis*; D018997:Chorionic Gonadotropin, beta Subunit, Human; D003433:Crosses, Genetic; D017931:DNA Primers; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D005810:Multigene Family; D009928:Organ Specificity; D010446:Peptide Fragments / Q000096:biosynthesis*; D010902:Pituitary Gland / Q000378:metabolism; D010920:Placenta / Q000378:metabolism*; D016133:Polymerase Chain Reaction / Q000379:methods; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D012313:RNA / Q000302:isolation & purification / Q000378:metabolism; D015183:Restriction Mapping
D006063:Chorionic Gonadotropin; D018997:Chorionic Gonadotropin, beta Subunit, Human; D017931:DNA Primers; D010446:Peptide Fragments; D012313:RNA