Expression of the β 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 α subunit differentiate into intermediates that coexpress the CGβ subunit. To study the regulation of expression of the CGβ genes in vivo, we constructed mice carrying a 36- kilobase cosmid insert containing the six CGβ 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 CGβ mRNA in mouse placenta was a function of gestational age; however, in contrast to the human placenta where CGβ peaks early in pregnancy, CGβ transcripts were only detectable in the mouse placenta late in gestation, i.e. from day 14 onward. Human CGβ was expressed also in cerebral cortex, pituitary, and at minute levels in adrenal. Pituitary CGβ expression was significantly lower than in placenta. Unexpectedly, transcripts were observed in cerebral cortex at levels comparable with the placenta. Most of the CGβ transcripts in mouse placenta are derived from CGβ genes 5, 3, and 8, in a ratio similar to that found in human placenta. In contrast, only CGβ genes 1 and 2 were transcribed in transgenic mouse brain; open reading frames from the CGβ1 and β2 transcripts differ substantially from the CGβ protein. The data show that although the mouse lacks a CGβ-like gene, the human CGβ 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 CGβ 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 CGβ gene cluster in vivo. Additionally, a different subset of CGβ genes (CGβ1 and β2) is active in the mouse brain.