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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 C...
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Published in: | The Journal of biological chemistry 1994-02, Vol.269 (7), p.4968-4973 |
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Main Authors: | , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | 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. |
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ISSN: | 0021-9258 1083-351X |
DOI: | 10.1016/S0021-9258(17)37640-8 |