MICE TRANSGENIC FOR THE HUMAN CARCINOEMBRYONIC ANTIGEN GENE MAINTAIN ITS SPATIOTEMPORAL EXPRESSION PATTERN

The tumor marker carcinoembryonic antigen (CEA) is predominantly expre ssed in epithelial cells along the gastrointestinal tract and in a var iety of adenocarcinomas. ks a basis for investigating its in vivo regu lation and for establishing an animal model for tumor immunotherapy, t ransgenic mice were generated with a 33-kilobase cosmid clone insert c ontaining the complete human CEA gene and Banking sequences. CEA was f ound in the tongue, esophagus, stomach, small intestine, cecum, colon, and trachea and at low levels in the lung, testis, and uterus of adul t mice of independent transgenic strains. CEA was first detected at da y 10.5 of embryonic development (embryonic day 10.5) in primary tropho blast giant cells and was found in the developing gut, urethra, trache a, lung, and nucleus pulposus of the vertebral column from embryonic d ay 14.5 onwards. From embryonic day 16.5 CEA was also visible in the n asal mucosa and tongue. Because this spatiotemporal expression pattern correlates well with that known for humans, it follows that the trans ferred genomic region contains all of the regulatory elements required for the correct expression of CEA. Furthermore, although mice apparen tly lack an endogenous CEA gene, the entire repertoire of transcriptio n factors necessary for correct expression of the CEA transgene is con served between mice and humans. After tumor induction, these immunocom petent mice will serve as a model for optimizing various forms of immu notherapy, using CEA as a target antigen.