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, cytotr ophoblasts expressing only the alpha subunit differentiate into interm ediates 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 approx imately 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 i n pregnancy, CG beta transcripts were only detectable in the mouse pla centa fate in gestation, i.e. from day 14 onward. Human CG beta was ex pressed also in cerebral cortex, pituitary, and at minute levels in ad renal. Pituitary CG beta expression was significantly lower than in pl acenta. Unexpectedly, transcripts were observed in cerebral cortex at levels comparable with the placenta. Most of the CG beta transcripts i n mouse placenta are derived from CG beta genes 5, 3, and 8, in a rati o similar to that found in human placenta. In contrast, only CG beta g enes 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 regu lated fashion in mouse placenta. Moreover, the stage-specific inductio n of the transgene suggests that mouse placental cells may express CG beta in an intermediate cell comparable with that seen in human placen ta. Taken together these data suggest that transgenic mice can be used as a model for elucidating the mechanisms involved in regulated expre ssion of the CG beta gene cluster in vivo. Additionally, a different s ubset of CG beta genes (CG beta 1 and beta 2) is active in the mouse b rain.