Mice Transgenic for the Human Carcinoembryonic Antigen Gene Maintain Its Spatiotemporal Expression Pattern

The tumor marker carcinoembryonic antigen (CEA) is predominantly
expressed in epithelial cells along the gastrointestinal tract and
in a variety of adenocarcinomas. As a basis for investigating its
in vivo regulation and for establishing an animal model for tumor
immunotherapy, transgenic mice were generated with a 33-kilobase
cosmid clone insert containing the complete human CEA gene and
flanking sequences. CEA was found in the tongue, esophagus,
stomach, small intestine, cecum, colon, and trachea and at low
levels in the lung, testis, and uterus of adult mice of independent
transgenic strains. CEA was first detected at day 10.5 of embryonic
development (embryonic day 10.5) in primary trophoblast giant cells
and was found in the developing gut, urethra, trachea, lung, and
nucleus pulposus of the vertebral column from embryonic day 14.5
onwards. From embryonic day 16.5 CEA was also visible in the nasal
mucosa and tongue. Because this spatiotemporal expression pattern
correlates well with that known for humans, it follows that the
transferred genomic region contains all of the regulatory elements
required for the correct expression of CEA. Furthermore, although
mice apparently lack an endogenous CEA gene, the entire repertoire
of transcription factors necessary for correct expression of the
CEA transgene is conserved between mice and humans. After tumor
induction, these immunocompetent mice will serve as a model for
optimizing various forms of immunotherapy, using CEA as a target
antigen.